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1

Crothers, Barbara A., Mohiedean Ghofrani, Chengquan Zhao, et al. "Low-Grade Squamous Intraepithelial Lesion or High-Grade Squamous Intraepithelial Lesion? Concordance Between the Interpretation of Low-Grade Squamous Intraepithelial Lesion and High-Grade Squamous Intraepithelial Lesion in Papanicolaou Tests: Results From the College of American Pathologists PAP Education Program." Archives of Pathology & Laboratory Medicine 143, no. 1 (2018): 81–85. http://dx.doi.org/10.5858/arpa.2018-0003-cp.

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Context.— Obtaining diagnostic concordance for squamous intraepithelial lesions in cytology can be challenging. Objective.— To determine diagnostic concordance for biopsy-proven low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) Papanicolaou test slides in the College of American Pathologists PAP Education program. Design.— We analyzed 121 059 responses from 4251 LSIL and HSIL slides for the interval 2004 to 2013 using a nonlinear mixed-model fit for reference diagnosis, preparation type, and participant type. We evaluated interactions between the reference diagnosis and the other 2 factors in addition to a repeated-measures component to adjust for slide-specific performance. Results.— There was a statistically significant difference between misclassification of LSIL (2.4%; 1384 of 57 664) and HSIL (4.4%; 2762 of 63 395). There was no performance difference between pathologists and cytotechnologists for LSIL, but cytotechnologists had a significantly higher HSIL misclassification rate than pathologists (5.5%; 1437 of 27 534 versus 4.0%; 1032 of 25 630; P = .01), and both were more likely to misrepresent HSIL as LSIL (P < .001) than the reverse. ThinPrep LSIL slides were more likely to be misclassified as HSIL (2.4%; 920 of 38 582) than SurePath LSIL slides (1.5%; 198 of 13 196), but conventional slides were the most likely to be misclassified in both categories (4.5%; 266 of 5886 for LSIL, and 6.5%; 573 of 8825 for HSIL). Conclusions.— More participants undercalled HSIL as LSIL (false-negative) than overcalled LSIL as HSIL (false-positive) in the PAP Education program, with conventional slides more likely to be misclassified than ThinPrep or SurePath slides. Pathologists and cytotechnologists classify LSIL equally well, but cytotechnologists are significantly more likely to undercall HSIL as LSIL than are pathologists.
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2

Goyal, Abha, Ami P. Patel, Thomas L. Dilcher, and Susan A. Alperstein. "Effects of Implementing the Dual Papanicolaou Test Interpretation of ASC-H and LSIL Following Bethesda 2014." American Journal of Clinical Pathology 154, no. 4 (2020): 553–58. http://dx.doi.org/10.1093/ajcp/aqaa069.

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Abstract Objectives To evaluate the impact of implementing the dual interpretation of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and low-grade squamous intraepithelial lesion (LSIL) after the Bethesda System 2014 and to compare it with other indeterminate interpretations. Methods Rates of high-risk human papillomavirus (HPV) positivity and histologic follow-up and the proportion of women with high-grade squamous intraepithelial lesion on histologic follow-up were compared for the combined interpretation of ASC-H and LSIL (ASCHL) and the categories of LSIL, cannot exclude high-grade squamous intraepithelial lesion (LSIL-H) and ASC-H. Results The percentage of ASCHL HPV-positive cases (86.0%) was similar to that of LSIL-H but significantly higher in comparison to that of ASC-H. The rates of cervical intraepithelial neoplasia grade 2 or higher (CIN 2+) and CIN 3+ for ASCHL (29.6% and 3.6%, respectively) were similar to those of LSIL-H and ASC-H. When stratified by HPV test results, the proportions of patients with CIN 2+ and CIN 3+ remained statistically similar to those with ASCHL and with LSIL-H and ASC-H. Conclusions Considering the similar risks of CIN 2+ and CIN 3+ for ASCHL and ASC-H, having a separate category of ASCHL for reporting cervical cytology appears to be redundant.
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Díaz López, Elsa, Gabriela Guarneros, Diana Mejía Morales, Juan Cristóbal Conde Pérez-Prina, Indra Elizalde Torres, and Alberto González Díaz. "Impact of Low-grade Intraepithelial Lesions with High-risk Human Papillomavirus (Part I)." Latin american journal of clinical sciences and medical technology 6, no. 1 (2024): 174–80. http://dx.doi.org/10.34141/ljcs8524095.

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One of the cervical cancer screening tests that has been prevalent in low- and mid-level income countries has been the cytology test, which uses a system of standardized reports such as the Bethesda. This system allows the detection of anomalies in squamous epithelial cells, including the squamous intraepithelial lesion (SIL), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), invasive squamous cell carcinoma, and adenocarcinoma. This categorization in two levels (LSIL and HSIL) has allowed to differentiate the carcinogenic potential of the human papillomavirus (HPV). LSIL are described as transient changes associated with an infection caused by HPV and asymptomatic infections with viral vacuolization within a two-year interval with no specific treatment. In case of HSIL, reference is made to its pre-cancer potential. Several factors have an impact in the onset of a LSIL: the presence of HPV (as one of the key etiologic agents) and other risk factors such as hormones, microbiome, first intercourse at early age, multiple sexual partners, other infections, immune status, and tobaco. All that contribute to the transient nature of the infection, or to its persistence, which in turn may promote the development and progression into an HSIL. The persistence of a high-risk HPV infection (HR-HPV) (or more rarely of low-grade too) plays an important role in the development of cervical cancer.
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Peng, Xinrui, Jiayuan Wan, Yafei Wang, and Liqun Wang. "Development of a clinical prediction model for pathological upgrading in low-grade squamous intraepithelial lesions following cervical conization." Cytojournal 21 (October 11, 2024): 37. http://dx.doi.org/10.25259/cytojournal_7_2024.

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Objective: This study aimed to identify key factors influencing post-operative pathologic escalation in Chinese women with histologic cervical low-grade squamous intraepithelial lesions (LSILs) undergoing cervical conization and construct a predictive nomogram model. Material and Methods: A retrospective analysis was conducted on 107 patients with LSIL from Bengbu City, Anhui Province, China, who underwent cervical conization at the First Affiliated Hospital of Bengbu Medical College from January 2019 to January 2023. Patients were categorized into groups based on post-operative pathological upgrade. Univariate and multivariate logistic regression analyses identified independent risk factors. A nomogram model was developed and evaluated for clinical predictive ability using calibration curves, the Hosmer–Lemeshow test, and decision curve analysis (DCA). Results: Post-operative pathological upgrades were experienced by 39.3% of patients with LSIL. Independent risk factors for escalation included positive human papillomavirus (HPV)16/18/52/53/58 high-risk types (P < 0.05, OR = 4.95, 95% CI = 1.32–18.46), ThinPrep Cytology Test (TCT) results indicating high-grade squamous intraepithelial lesion (HSIL)/atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion (ASC-H)/atypical glandular cells ( AGC) (P < 0.01, OR = 13.12, 95% CI = 3.10–55.50), and cervical transformation zone (TZ) type III (P < 0.05, OR = 6.10, 95% CI = 1.65–22.56). Based on these factors, the nomogram demonstrated good differentiation and calibration (area under the curve [AUC]: 0.744, 95% CI: 0.674–0.839). DCA indicated high clinical predictive value. Conclusion: HPV16/18/52/53/58 high-risk types, TCT HSIL/ASC-H/AGC, and colposcopic cervical TZ type III are independent risk factors for post-operative pathologic escalation in LSIL. Consideration of pre-operative HPV, TCT results, and cervical TZ type is crucial for effective triage and patient management. The constructed nomogram provides a practical tool for risk assessment of patients with LSIL undergoing cervical conization.
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Li, Yilan, Olubunmi Shoyele, and Vinod B. Shidham. "Pattern of cervical biopsy results in cases with cervical cytology interpreted as higher than low grade in the background with atrophic cellular changes." Cytojournal 17 (May 16, 2020): 12. http://dx.doi.org/10.25259/cytojournal_82_2019.

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Objective: The cytomorphological changes associated with atrophic cellular pattern (ACP) in cervical cytology smears may mimic high-grade squamous intraepithelial lesion (HSIL). Due to this, there may be higher chances of cytomorphological overinterpretation in cases with ACP. Estrogen therapy (ET) (topical or systemic) would reverse the changes related to atrophy and repeat Pap smear after ET should correct the false positives. This approach would minimize the unindicated invasive interventions. However, performing immediate biopsies following “higher than low-grade squamous intraepithelial lesion (LSIL) (atypical squamous cells-cannot exclude HSIL, low-grade squamous intraepithelial lesions-cannot exclude HSIL, and HSIL) interpretations” in such cases, is a general trend. Pap smears with “higher than LSIL interpretations” in association with ACP over a period of 10 years were selected. Materials and Methods: A total of 657,871 cases over 10 years were reviewed, of which 188 Pap smears interpreted as higher than LSIL interpretations with ACP were selected randomly for this study. Result: Of these 188 cases, 67 underwent biopsies which were reviewed and compared with 67 biopsies performed for “higher than LSIL interpretation” cases without ACP. The follow-up biopsy material was reviewed including elective p16 immunohistochemistry with other clinical details including high-risk HPV test results as indicated. Conclusion: The findings demonstrated that Pap smears with ACP have higher false positives due to tendency for cytomorphologic overinterpretation as compared to non-ACP group.
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Kaya Terzi, Neslihan, and Ozden Yulek. "Assessment of Cervicovaginal Smear and HPV DNA Co-Test for Cervical Cancer Screening: Implications for Diagnosis and Follow-Up Strategies." Diagnostics 14, no. 6 (2024): 611. http://dx.doi.org/10.3390/diagnostics14060611.

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Objective: Cervical cancer is a major cause of cancer-related mortality, necessitating effective screening and diagnostic methods. This study aimed to assess the performance of cervicovaginal smear (CVS) and human papillomavirus (HPV)-DNA co-test. Study design: The pathology results of 225 female patients who underwent HPV-DNA testing with CVS between 2014 and 2022 and were subsequently diagnosed by colposcopic cervical biopsy or second CVS were retrospectively analyzed. Results: CVS samples showed atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and cervical cancer. Concordance between the first and second diagnoses demonstrated moderate agreement for LSIL. ASCUS cases exhibited a significant correlation with HPV-DNA positivity and higher-grade cervical lesions. In biopsy, sensitivity and specificity for CIN1/LSIL were 87.5% and 53.3, respectively, while for CIN2-3/HSIL, they were 83.87% and 58.49%. HPV testing showed significant correlation with histopathologic results. In women over 40 years, more intraepithelial lesions were diagnosed compared to younger women (p < 0.005). The conventional smear technique proved reliable in detecting high-grade lesions. Conclusions: Despite the limitations of our study, our results emphasize the value of HPV-DNA testing to avoid unnecessary interventions and to establish appropriate follow-up strategies.
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Mishra, Jaya, Sweety Kalantri, Vandana Raphael, Biswajit Dey, Yookarin Khonglah, and Ananya Das. "Prevalence of human papillomavirus infection in abnormal pap smears." Cytojournal 20 (August 29, 2023): 21. http://dx.doi.org/10.25259/cytojournal_8_2021.

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Objectives: This study was undertaken to study the prevalence of human papillomavirus (HPV) infection using the polymerase chain reaction (PCR) technique in abnormal cervical pap smears and to correlate the different cytological results with HPV infection. Material and Methods: A total of 1788 cervical pap smears of women more than 30 years of age conducted over a period of 1 year 3 months (June 2015–August 2016) were screened by liquid-based cytology. High-risk (HR)-HPV testing was performed by PCR in abnormal lesions. Inflammatory smears and some atypical squamous cells of undetermined significance (ASCUS)-reactive cases were excluded from HPV testing. Histopathological correlation was done wherever possible. Results: The overall prevalence of the intraepithelial lesions/malignancy was ASCUS. (ASCUS) - 79 (4.42%), atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) - 10 (0.56%), low-grade squamous intraepithelial lesion (LSIL) - 26 (1.45%), high-grade squamous intraepithelial lesion (HSIL) - 15 (0.84%), squamous cell carcinoma - 5 (0.28%), and adenocarcinoma - 1 case (0.06%). Overall, 136 (7.60%) samples were classified as abnormal. Seventy-seven samples were included for HR-HPV testing – 20 ASCUS, 10 ASC-H, 26 LSIL, 15 HSIL, and 6 malignant cases. A control group of ten samples with normal cervical cytology within the normal limit (Control) (WNLc) was tested for HR-HPV. HR-HPV was detected in 20% of samples of the WNLc group, 45% of the ASCUS group, 70% of the ASC-H group, 73.07% of the LSIL group, 86.67% of the HSIL, and 83.34% of the samples in the malignant group. Overall, HR-HPV was detected in 68.83% of abnormal cervical pap smears. Conclusion: Our study shows that the percentage of HR-HPV-positive case increases with the severity of cytologic morphology. HPV had 4 times higher positivity in squamous intraepithelial lesion as compared to ASCUS.
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Zhao, Chengquan, Shuping Zhao, Amer Heider, and R. Marshall Austin. "Significance of High-Risk Human Papillomavirus DNA Detection in Women 50 Years and Older With Squamous Cell Papanicolaou Test Abnormalities." Archives of Pathology & Laboratory Medicine 134, no. 8 (2010): 1130–35. http://dx.doi.org/10.5858/2009-0624-oa.1.

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Abstract Context.—Data on cytologic screening and follow-up disproportionately reflect findings from frequently screened younger women, and data from screened women 50 years and older using newer screening technologies remain limited. Objective.—To better understand the utility of adjunctive high-risk human papillomavirus (hrHPV) testing for disease risk stratification in women 50 years and older with a range of liquid-based cytology, abnormal, squamous cell Papanicolaou test results. Design.—Liquid-based cytology cases interpreted as high-grade squamous intraepithelial lesion (HSIL); low-grade squamous intraepithelial lesion (LSIL); atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H); and atypical squamous cells of undetermined significance (ASC-US) at Magee-Womens Hospital (Pittsburgh, Pennsylvania) were retrospectively identified for a 36-month period between July 1, 2005, and June 30, 2008, from women 50 years and older who also had hrHPV DNA test results. Histopathologic follow-up diagnoses were analyzed. Results.—During the study period, 4855 women 50 years and older had HSIL, LSIL, ASC-H, or ASC-US Papanicolaou test results and hrHPV testing. In 89.3% of HSIL cases, 71.0% of LSIL cases, 38.9% of ASC-H cases, and 14.2% of ASC-US cases, hrHPV test results were positive. The positive predictive value of a positive hrHPV test for histopathologic cervical intraepithelial neoplasia 2/3+ detection was 90.5% with HSIL, 15% with ASC-H, 9.8% with LSIL, and 3.2% with ASC-US. A negative hrHPV test result had a 100% negative predictive value for histopathologic cervical intraepithelial neoplasia 2/3+ in both LSIL and ASC-H cases. Conclusions.—In women 50 years and older, a positive hrHPV test result significantly increased the likelihood of follow-up histopathologic diagnoses of cervical intraepithelial neoplasia 2 /3+ in patients with HSIL, LSIL, and ASC-H Papanicolaou test results compared with women with negative hrHPV test results. No cervical intraepithelial neoplasia 2/3+ diagnoses were documented in women 50 years and older with LSIL or ASC-H Papanicolaou test results and negative hrHPV test results.
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Gbinigie, Eronmwon E., Joshua Fogel, and Maggie Tetrokalashvili. "Low Utility in Colposcopy-directed Biopsies for Non-high Grade Cytological Abnormalities on PAP Smear." Current Women s Health Reviews 16, no. 1 (2020): 18–22. http://dx.doi.org/10.2174/1573404815666190821093421.

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Background: Clinicians commonly perform colposcopy directed biopsies on patients with low grade squamous intraepithelial lesion (LSIL) on PAP cytology even when not consistent with clinical guidelines. Objective: We study the association of PAP cytology screening results with cervical intra-epithelia neoplasia (CIN) 2-3 high-grade dysplasia, as confirmed by colposcopy-directed biopsy. Methods: A retrospective study of 263 women with an abnormality on the PAP smear. Multinomial logistic regression was performed with predictors of PAP cytology screening results with the outcome variable of colposcopy-directed biopsy. Results: High grade squamous intraepithelial lesion (HSIL) had significantly increased relative risk for CIN 2-3 (RR: 9.85, 95% CI: 1.84, 52.79, p=0.008). LSIL was not significantly associated with CIN 2-3. In the comparisons of negative with CIN-1, both HSIL and LSIL were not significantly associated with a negative biopsy. Conclusion: HSIL is associated with cervical dysplasia of CIN 2-3 while LSIL is not associated with cervical dysplasia of CIN 2-3. We do not recommend routine biopsies in patients with LSIL cytologic abnormalities unless additional compelling factors exist.
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Parwanto, ML Edy. "Kanker serviks dan gen Fas-promoter-670." Jurnal Biomedika dan Kesehatan 2, no. 3 (2019): 90–91. http://dx.doi.org/10.18051/jbiomedkes.2019.v2.90-91.

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Kanker serviks merupakan keganasan pada serviks. Jenis kanker tersebut terjadi pada perempuan dan masih menjadi masalah di Indonesia. Indonesia merupakan negara urutan ke 4 di Asia Tenggara dengan insiden kanker serviks terbesar setelah Kamboja, Myanmar dan Thailand. Berdasar data statistik tahun 2012, tingkat insidensi (incidence rate) kanker serviks di Indonesia 17 per 100.000 perempuan per tahun.(1)
 Telah terbukti bahwa penyebab primer terjadinya kanker serviks yaitu virus papilloma atau yang lebih dikenal dengan istilah “human papillomavirus (HPV)”. Terdapat beberapa jenis serotype HPV, tetapi tidak semua jenis serotype bersifat progesif menjadikan kanker serviks. Salah satu serotype yang bersifat progesif menjadikan kanker serviks yaitu HPV serotype 16. HPV serotype 16 mampu mengubah sel epitel squamosa serviks (cervical-squamous-epithelial cells=CSEC) normal menjadi lesi intraepitelial squamosa tingkat rendah (low-grade squamous intraepithelial lesion=LSIL) atau neoplasia intraepitel serviks (cervical intraepithelial neoplasia=CIN) 1. Selanjutnya, LSIL atau CIN 1 berkembang menjadi lesi intraepitelial squamosa tingkat tinggi (high-grade squamous intraepithelial lesion=HSIL) atau CIN 2, dan akhirnya menjadi kanker serviks yang invasif (invasive cervical cancer=CIN3).(2)
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Mehlhorn, Grit, Carla Schulmeyer, Martin Koch, Simone Renner, Paul Gaß, and Matthias Beckmann. "Diagnostik und Therapie des Vulvakarzinoms." Der Klinikarzt 46, no. 05 (2017): 212–16. http://dx.doi.org/10.1055/s-0043-109596.

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Mit einer Inzidenz von 5,8/100 000 Frauen/Jahr ist das Vulvakarzinom das vierthäufigste Genitalkarzinom der Frau. Meist werden Vulvakarzinome in einem frühen Stadium diagnostiziert. Häufigstes Symptom ist der therapieresistente Pruritus, perineale Schmerzen und/oder beim Sitzen, Dysurie und Brennen. Bei der klinischen Inspektion sollte das komplette äußere Genitale mit Vagina, Perineum, Anus sowie die Zervix inspiziert werden. Liegt eine VIN1, LSIL (vulväre intraepitheliale Neoplasie Grad 1, low-grade squamous intraepithelial lesion) ohne Symptome vor, sind regelmäßige Kontrollen ausreichend. Bei symptomatischer LSIL, HPV-assoziierter VIN2 oder VIN3 (vulväre intraepitheliale Neoplasie Grad 2 oder 3, high-grade squamous intraepithelial lesion) kann eine Laserevaporisation erfolgen. Eine komplette Vulvektomie sollte nur bei multizentrischen Tumoren erfolgen. Eine systematische Lymphonodektomie ist ab Stadium T1b mit Infiltrationstiefe > 1 mm empfohlen. Eine adjuvante Radiotherapie der Primärtumorregion sollte bei non-in-sano-Situation durchgeführt werden, falls eine Nachresektion aus funktionellen Gründen oder Patientenwunsch nicht möglich ist. Eine lebenslange Nachsorge ist notwendig, denn jede dritte Patientin mit Vulvakarzinom erleidet ein Rezidiv. Als Therapie des Lokalrezidivs ohne Beteiligung von Anus, Urethra oder Lymphknoten sollte eine operative Resektion mit R0-Situation angestrebt werden.
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Tawfik, Ossama, Marilyn Davis, Susan Dillon, et al. "Whole-Slide Imaging of Pap Cellblock Preparations Is a Potentially Valid Screening Method." Acta Cytologica 59, no. 2 (2015): 187–200. http://dx.doi.org/10.1159/000430082.

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Objective: To date, the impact of digital imaging on routine cytology remains far from perfect. Cellblock (CB) preparations from Pap samples have been shown to be diagnostically valuable. We evaluated the validity of utilizing whole-slide imaging (WSI) prepared from Pap CBs as a screening tool. Study Design: A total of 1,110 CB slides prepared from residual Pap samples were analyzed - 563 normal, 282 atypical squamous cells of undetermined significance (ASCUS), 12 atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion, 188 low-grade squamous intraepithelial lesions (LSIL), 36 high-grade squamous intraepithelial lesions (HSIL), 25 atypical glandular cells of undetermined significance, 1 adenocarcinoma in situ, 2 invasive adenocarcinomas, and 1 squamous cell carcinoma. Virtual slides were obtained using the Aperio system. Test performance characteristics of liquid-based samples and WSI from CB samples were compared. Results: Average sensitivity and specificity of the five WSI reviewers was 58.3 and 85.1% for ASCUS, respectively, 54.1 and 93.9% for LSIL, and 51.8 and 98.8% for HSIL. Overall WSI sensitivity and specificity for detecting lesions was 82.1 and 86.2%, respectively. Agreement (kappa values) between WSI reviewers was 0.56 for ASCUS, 0.69 for LSIL, 0.67 for HSIL, and 0.74 for negative samples. Conclusions: WSI of CB preparations is a feasible method to achieve high-quality specimen preparations. It is as sensitive as liquid-based methods and appears to be highly specific for the detection of LSIL and HSIL.
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Yang, Xue, Ling He, Xiao Xiao, et al. "Effectiveness of TruScreen for detecting CIN2+ in women with ThinPrep cytologic test results indicating atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions." Future Oncology 19, no. 37 (2023): 2493–504. http://dx.doi.org/10.2217/fon-2023-0297.

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Objective: To evaluate the effectiveness of TruScreen (TS) for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with abnormal ThinPrep cytologic test (TCT) results. Methods: 466 women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) were enrolled and underwent TS, colposcopy and biopsy examination. Results: Compared with the high-risk human papillomavirus (hrHPV) test for CIN2+, significantly higher specificity of TS, combined TS and hrHPV (69.6 and 75.0 vs 36.8% in ASCUS; 59.0 and 69.9 vs 30.1% in LSIL), significantly higher positive predictive value of combined TS and hrHPV were observed (32.7 vs 24.6% in ASCUS; 47.9 vs 35.6% in LSIL). Conclusion: TS combined with hrHPV showed better performance in diagnosing CIN2+ in ASCUS/LSIL.
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Youssef, M., S. Canete-Portillo, A. Yemelyanova, and B. Ronnett. "Patterns of Cytokeratin 7 Expression in Cervical Squamous Intraepithelial Lesions." American Journal of Clinical Pathology 154, Supplement_1 (2020): S37. http://dx.doi.org/10.1093/ajcp/aqaa161.077.

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Abstract Introduction/Objective It has been suggested that cervical high-grade squamous intraepithelial lesions (HSIL/CIN2-3) arise from squamocolumnar junction cells that express cytokeratin 7 (CK7). Significant CK7 expression (gradation or full-thickness) has been proposed as a marker of progression of low-grade squamous intraepithelial lesions (LSIL/CIN1) to HSIL and of persistence of HSIL/CIN2. The goal of the study is to survey patterns of CK 7 expression in the different grades of squamous intraepithelial lesions (SILs). Methods 65 cervical specimens (biopsies and excisions) containing 95 lesions of different grades were assessed by immunohistochemical analysis (IHC) for CK7 expression. 26 cases contained more one lesion grade. The diagnosis of HSIL (CIN2-3) was confirmed by p16 IHC. CK7 expression was scored negative, patchy, gradation (i.e., top-down), or full-thickness pattern. In cases with heterogeneous staining, the strongest pattern was used for analysis. Results There was significant variation in patterns within morphologically contiguous lesional foci; staining heterogeneity was noted in 42% of cases. All patterns of expression were encountered in all lesion grades. LSIL/CIN1 (n=47), either alone (n=27) or in combination with HSIL (n=20), often lacked CK7 expression (53%) or were patchy (17%). The frequency of significant (gradation or full-thickness) CK7 expression in LSIL with concomitant HSIL was greater than LSIL occurring alone (40% vs. 22%, respectively). HSIL/CIN3 (n=19) was dominated by full-thickness expression (57%). HSIL/CIN2 (n=29) had a very heterogeneous spectrum of expression with 34% of cases lacking expression. Conclusion CK7 expression is variable across all grades of SILs. LSIL with concomitant HSIL was associated with significant CK7 expression more frequently than LSIL alone. Significant proportion of HSIL, particularly CIN2, lacks CK7 expression. Given this variability, caution is advised regarding the use of CK7 expression as a marker of progression.
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Shidham, Vinod B., Nidhi Kumar, Raj Narayan, and Gregory L. Brotzman. "Should LSIL with ASC-H (LSIL-H) in cervical smears be an independent category? A study on SurePath™ specimens with review of literature." CytoJournal 4 (March 20, 2007): 7. http://dx.doi.org/10.1186/1742-6413-4-7.

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Background Cervical smears exhibiting unequivocal features of ‘low grade squamous intraepithelial lesion’ (LSIL) are occasionally also admixed with some cells suspicious for, but not diagnostic of, ‘high grade squamous intraepithelial lesion’ (HSIL). Only a few studies, mostly reported as abstracts, have evaluated this concurrence. In this study, we evaluate the current evidence that favors a distinct category for “LSIL, cannot exclude HSIL” (LSIL-H), and suggest a management algorithm based on combinations of current ASCCP guidelines for related interpretations. Methods We studied SurePath™ preparations of cervical specimens from various institutions during one year period. Cytohisto correlation was performed in cases with cervical biopsies submitted to our institution. The status of HPV DNA testing was also noted in some LSIL-H cases with biopsy results. Results Out of 77,979 cases 1,970 interpreted as LSIL (1,523), LSIL-H (146), ‘atypical squamous cells, cannot exclude HSIL’ (ASC-H) (109), and HSIL (192) were selected. Concurrent biopsy results were available in 40% (Total 792 cases: 557 LSIL, 88 LSIL-H, 38 ASCH, and 109 HSIL). Biopsy results were grouped into A. negative for dysplasia (ND), B. low grade (HPV, CIN1, CIN1 with HPV), and C. high grade (CIN 2 and above). The positive predictive values for various biopsy results in relation to initial cytopathologic interpretation were: a. LSIL: (557 cases): ND 32% (179), low grade- 58% (323), high grade- 10% (55); b. LSIL-H: (88 cases): ND 24% (21), low grade- 43% (38), high grade- 33% (29); c. ASCH: (38 cases): ND 32% (12), low grade- 37% (14), high grade- 31% (12); d. HSIL (109 cases): ND 5% (6), low grade 26% (28), high grade 69% (75). The patterns of cervical biopsy results in cases reported as LSIL-H were compared with that observed in cases with LSIL, ASC-H, and HSIL. 94% (32 of 34) of LSIL-H were positive for high risk (HR) HPV, 1 was negative for HR HPV but positive for low risk (LR), and 1 LSIL-H was negative for HR and LR both. Conclusion LSIL-H overlapped with LSIL and ASC-H, but was distinct from HSIL. A management algorithm comparable to ASC-H and HSIL appears to be appropriate in LSIL-H cases.
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Ivanova, Yonka, Yavor Kornovski, Stoyan Kostov, Stanislav Slavchev, Dimitar Metodiev, and Angel Yordanov. "Prognostic factors for low- and high grade squamous intraepithelial lesions in histological preparations following LLETZ procedure." Wiadomości Lekarskie 77, no. 8 (2024): 1562–68. http://dx.doi.org/10.36740/wlek202408105.

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Aim: To investigate the influence of the following prognostic factors: age, parity, hormonal status (premenopausal, postmenopausal), histological result from targeted biopsy (LSIL, HSIL), adequacy of colposcopic examination (satisfactory, unsatisfactory colposcopy), type of TZ (type 1, 2, 3), type of cervical lesions (type 1, 2, 3), the colposcopic impression (diagnosis) of the cervical lesion (LSIL, HSIL/Ca colli uteri in situ), lesion size (up to 1/3; up to 2/3; more than 2/3 of the cervical circumference) for the occurrence of LSIL and HSIL/Ca colli uteri in situ in the final histological result after LLETZ procedure. Materials and Methods: This is a prospective study (01.01.2017 – 31.07. 2021) including 189 patients with cervical precancerous lesions received LLETZ treatment One gynaecologic oncologist performed video colposcopy, targeted biopsy, and LLETZ. One histopathologist diagnosed histological specimens from the biopsy and LLETZ procedure Results: We found a statistically significant correlation between the histological result of the targeted biopsy factor and the colposcopic diagnosis factor concerning the final histological result of LLETZ. The cervical lesion size factor and cervical lesion type factor have prognostic significance for the histological outcome following LLETZ. Conclusions: The histological result of targeted biopsy and colposcopic diagnosis are significant factors for the final histological result after LLETZ. Cervical lesion invasion into the endocervical canal is a prognostic factor for HSIL, and its invisible borders – for carcinoma (in situ or microinvasive/invasive). Lesion size up to 1/3 of the cervix is a prognostic factor for LSIL and large lesions (2/3 of the cervix) – for HSIL and cervical cancer (in situ, microinvasive/invasive).
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Zhang, Fred Fangyuan, Helen Whitler Banks, Shanna Maria Langford, and Diane Davis Davey. "Accuracy of ThinPrep Imaging System in Detecting Low-Grade Squamous Intraepithelial Lesions." Archives of Pathology & Laboratory Medicine 131, no. 5 (2007): 773–76. http://dx.doi.org/10.5858/2007-131-773-aotisi.

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Abstract Context.—The ThinPrep Imaging System (Imager) for cervical cytology is used in many US laboratories, but the ability of the system to identify classic changes of low-grade squamous intraepithelial lesion (LSIL) has not been independently reported. Objective.—To evaluate the accuracy of this system in detecting classic LSIL cells. Design.—A total of 114 imaged ThinPrep LSIL cases from April to June 2005 were reviewed to determine whether the most diagnostically relevant cells were present in the 22 fields selected by Imager. Those LSIL specimens from January to June 2005 that were initially screened by the Imager and classified as “negative” in the 22 fields were also reviewed. The average number of classic koilocytes per slide was compared among cases that had koilocytes within 22 fields with cases upgraded during full review. Results.—Twelve (10.5%) of 114 LSIL cases from April to June 2005 did not show diagnostic LSIL cells within the initial 22 fields. Full manual rescreening was performed on 1025 cases from January to June (20.4% of negative cases). Nine cases that were initially negative in the 22 fields were revised to LSIL (2.4% of all 381 LSIL cases reported from January to June 2005). An average of 10 to 11 koilocytes were present in these 2 groups, which was significantly lower than the average of 75 koilocytes in cases in which the 22 Imager-selected fields showed LSIL. Conclusions.—Although the ThinPrep Imager finds abnormal cells in most LSIL cases, the system may have limitations in detecting koilocytes in the 22 Imager-selected fields. When 10% quality control rescreening is performed as required by federal regulations, full manual rescreening will provide the most accurate results.
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Faqih, Layla, Lama Alzamil, Esraa Aldawood, et al. "Prevalence of Human Papillomavirus Infection and Cervical Abnormalities among Women Attending a Tertiary Care Center in Saudi Arabia over 2 Years." Tropical Medicine and Infectious Disease 8, no. 12 (2023): 511. http://dx.doi.org/10.3390/tropicalmed8120511.

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Human papillomavirus (HPV) genotype distribution varies according to the assessment method and the population targeted. This study aimed to assess HPV infection prevalence in women aged 23 to 82 with abnormal cytology attending King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, using retrospective data collected from January 2021 to December 2022. Cytological distribution included 155 samples of atypical squamous cells of undetermined significance (ASCUS) (n = 83), low-grade squamous intraepithelial lesion (LSIL) (n = 46), high-grade squamous intraepithelial lesion (HSIL) (n = 14), atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) (n = 10), and squamous cell carcinoma (SCC) (n = 2). All samples were submitted to HPV detection and genotyping using Xpert HPV assay specimens. The most prevalent epithelial abnormalities were ASCUS (53.50%). Positive HPV infection results were observed in 52.9% of the samples. The highest prevalence of HPV genotypes, accounting for 31%, was attributed to the other high-risk genotypes, including 31, 33, 35, 39, 51, 52, 56, 58, 59, 66, and 68, followed by high-risk genotype 16, which counted in 11.60% of cases. Individuals who tested positive for HPV 16 were at a high risk of ASC-H, HSIL, and LSIL. Those testing positive for HPV 18–45 exhibited an elevated risk of LSIL, and those with positive results for other high-risk HPV genotypes were at an increased risk of ASCUS and LSIL, suggesting a low oncogenic potential. The results suggest that the percentage of association between samples with abnormal cervical presentation and negative high-risk HPV diagnosis is noticeably increasing. This underscores the need for effective screening programs and an understanding of the impact of specific HPV genotypes on cervical abnormalities.
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Zakharova, N. M., O. N. Vetchinnikova, and A. B. Zulkarnaev. "Cytological features of crypt involvement by cervical intraepithelial neoplasia." Voprosy ginekologii, akušerstva i perinatologii 20, no. 4 (2021): 22–28. http://dx.doi.org/10.20953/1726-1678-2021-4-22-28.

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Objective. To determine the cytological criteria of crypt lesion by cervical intraepithelial neoplasia (CIN). Patients and methods. The retrospective cohort study included 76 women who underwent a comprehensive medical evaluation after screening tests: cervical cytology test, colposcopy, biopsy and histological examination of the cervix, polymerase chain reaction (PCR) test for human papillomavirus (HPV). Cytological material was obtained using an endocervical brush (Cytobrush); it was stained by the Pappenheim method and examined by light microscopy; the Bethesda system was used. Results. Cytological examination of the cervical smears (cervical ectopy and endocervix) in 59 (78%) women revealed squamous epithelial cells with features typical for dysplasia of different severity: mild – LSIL (low-grade squamous intraepithelial lesions) and severe – HSIL (high-grade squamous intraepithelial lesion). Smears of 31 (53%) women also showed cylindrical (glandular) epithelial cells with signs of pronounced proliferation: 2 (9.5%) with LSIL and 29 (76.3%) with HSIL. Histological examination of the cervix in all 59 women revealed dysplasia of varying severity. Features of endocervical crypt involvement were detected in 28 women: 1 (4.8%) with LSIL and 27 (71.1%) with HSIL. The sensitivity and specificity of cytological diagnosis of cervical crypt involvement in LSIL were 100 and 95%, in HSIL – 87 and 67%, respectively. Conclusion. The cytological feature of crypt involvement by CIN is the presence in cervical mucus smears of clusters and papillary structures of proliferating, immature cylindrical epithelial cells, partially with cellular and nuclear polymorphism. Key words: crypts, cervical intraepithelial neoplasia, cytological examination
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Rahman, Mohammed Mustafizur, Shabnam Imam, Mst Sayedatun Nessa, Joyosree Saha, Farhana Islam, and Abu Khalid Muhammad Maruf Raza. "Pap smear in women with leucorrhea : Experience in a tertiary medical college hospital of Bangladesh." Northern International Medical College Journal 9, no. 1 (2018): 252–54. http://dx.doi.org/10.3329/nimcj.v9i1.35921.

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Background : Poor genital hygiene has been responsible for high prevalence of excessive vaginal discharge. Leucorrhoea is the clinical evidence of infection and can be treated satisfactorily whenever diagnosed. Occurrence of various cervical epithelial lesion associated with discharge can be easily prevented if detected early. Majority of the patients with various cervical epithelial lesion attending in the hospital present with varying degree of vaginal discharge and cytological cellular aberrations in the cervical epithelium.Objective : The aim of the present study is to observe the various patterns of cervical epithelial lesions in cytopathology and associated infections in patients with Leucorrhoea.Methodology : This observational study was done over a period of ten months in Popular Medical college hospitals of Bangladesh. A total of 230 cases were included in the study with women of age range 15-45 years, complaining of leucorrhoea. After a thorough vaginal examination Pap smears were taken and immediately fixed in absolute alcohol and stained according to the papanicolaous technique. The cytopathological changes observed in the cervical smears were graded according to the Bethesda system for reporting cervical cytology.Results : Out of 230 cases the cytological patterns were found Normal in 4 (1.7%), Inflammatory 204 (88.3%), Low grade squamous intraepithelial (LSIL)10 (4.8%), High grade squamous intraepithelial (HSIL) 6(2.6%), Atypical squamous cells of undetermined significance (ASCUS) 6 (2.6%) and the distribution of different types of pathogens detected were Trichomonas 33 (70.62%), Candida albicans 19 (40.66%).Conclusion : In this study significant numbers of Leucorrhoea patients were detected with cervical squamous intraepithelial lesions (SIL) in which LSIL (Low grade squamous intraepithelial) was higher. Associated infections were Trichomonas and Candida albicans. Therefore cytological screening for early detection of cervical squamous intraepithelial lesion is essential routine medical examination for Leucorrhoea patients in gynaecological practice.Northern International Medical College Journal Vol.9(1) July 2017: 252-254
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Prasetyo, Rizki Eko, Gondo Mastutik, and Sjahjenny Mustokoweni. "PREVALENCE OF HUMAN PAPILLOMAVIRUS GENOTYPES IN LOW AND HIGH GRADE SQUAMOUS INTRAEPITHELIAL LESIONS AT CERVICAL TISSUE." Folia Medica Indonesiana 53, no. 4 (2017): 258. http://dx.doi.org/10.20473/fmi.v53i4.7157.

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HPV infection is known to cause cervical cancer. This study aimed to identify the variant of HPV genotypes of cervical precancerous lesions from low grade squamous intraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL). This was an explorative study using formalin fix paraffin embedded (FFPE) from cervical precancerous lesions at Dr. Soetomo Hospital, Surabaya. DNA was extracted from FFPE and hybridized for HPV genotyping using Ampliquality HPV Type Express kit (AB ANALITICA) by reverse line blot techniques. The results showed that there were variants of HPV genotype in LSIL. The variants were HPV16 (8/15), HPV18 (3/15), HPV52 (1/15), HPV6+31 (1/15), HPV6+18 (1/15), and HPV72+68 (1/15), and in HSIL which were HPV16 (4/10), HPV18 (2/10), HPV59 (1/10), HPV6+45 (1/10), HPV61+26 (1/10), and HPV16+31 (1/10). The characteristics of infection in LSIL were single infection of high-risk (hr) HPV and multiple infection of low-risk (lr)+hr HPV, and in HSIL were single infection of HPVhr, multiple infection of HPVhr+hr and HPVlr+hr. In conclusion, HPV prevalence in cervical precancerous lesions is single infection by HPV16 (48%), HPV18 (20%), HPV52 (4%), HPV59 (4%), and multiple infection by HPV6+31, HPV6+18, HPV6+45, HPV16+31, HPV61+26, HPV72+68 is 4%.
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Pakharukova, Mariya I., Irina G. Starodubova, Yulia G. Lagereva, and Yakov B. Beikin. "Specific distribution of human papillomavirus type in patients of different reproductive age with low and high-grade squamous intraepithelial lesion." Journal of Ural Medical Academic Science 18, no. 4 (2021): 282–94. http://dx.doi.org/10.22138/2500-0918-2021-18-4-282-294.

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The purpose of this work was to study the characteristics of human papillomaviruses spread in reproductive age patients with low and high degree squamous intraepithelial lesions of the cervix in Yekaterinburg. Material and Methods. In with study 140 female patients of reproductive age with histologically confirmed low and high grade intraepithelial lesions were retrospectively included. HPV-genotyping by polymerase chain reaction was carried out in combination with liquid-based cytology BDSurePath. Formed 4 groups: LSIL, age from 18 to 30 years; LSIL, age from 31 to 44; HSIL, ages 18 to 30; HSIL, ages 31 to 44. Results. Analysis of the obtained data demonstrated that HPV 16 prevails in intraepithelial squamous cell lesions of the cervix of low and high degree in women of reproductive age in Yekaterinburg. In women aged 18-30 years, compared with the older reproductive age (31-44 years), multiple infections with 3, 4 or more HPV genotypes are more often recorded, regardless of the degree of damage. In addition to HPV 16, low-grade lesions in young women are most often associated with HPV 31, 51, and 52, and high-grade lesions with types 31, 33 and 52. HPV 33 is characteristic of a high degree of intraepithelial squamous cell lesions, especially in patients of older reproductive age. With intraepithelial squamous lesions of low and high degree, regardless of age, an equally high concentration of HPV DNA is observed.
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Pakharukova, Mariya I., Irina G. Starodubova, Yulia G. Lagereva, and Yakov B. Beikin. "Specific distribution of human papillomavirus type in patients of different reproductive age with low and high-grade squamous intraepithelial lesion." Journal of Ural Medical Academic Science 18, no. 4 (2021): 282–94. http://dx.doi.org/10.22138/2500-0918-2021-18-4-282-294.

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The purpose of this work was to study the characteristics of human papillomaviruses spread in reproductive age patients with low and high degree squamous intraepithelial lesions of the cervix in Yekaterinburg. Material and Methods. In with study 140 female patients of reproductive age with histologically confirmed low and high grade intraepithelial lesions were retrospectively included. HPV-genotyping by polymerase chain reaction was carried out in combination with liquid-based cytology BDSurePath. Formed 4 groups: LSIL, age from 18 to 30 years; LSIL, age from 31 to 44; HSIL, ages 18 to 30; HSIL, ages 31 to 44. Results. Analysis of the obtained data demonstrated that HPV 16 prevails in intraepithelial squamous cell lesions of the cervix of low and high degree in women of reproductive age in Yekaterinburg. In women aged 18-30 years, compared with the older reproductive age (31-44 years), multiple infections with 3, 4 or more HPV genotypes are more often recorded, regardless of the degree of damage. In addition to HPV 16, low-grade lesions in young women are most often associated with HPV 31, 51, and 52, and high-grade lesions with types 31, 33 and 52. HPV 33 is characteristic of a high degree of intraepithelial squamous cell lesions, especially in patients of older reproductive age. With intraepithelial squamous lesions of low and high degree, regardless of age, an equally high concentration of HPV DNA is observed.
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Pakharukova, Mariya I., Irina G. Starodubova, Yulia G. Lagereva, and Yakov B. Beikin. "Specific distribution of human papillomavirus type in patients of different reproductive age with low and high-grade squamous intraepithelial lesion." Journal of Ural Medical Academic Science 18, no. 4 (2021): 282–94. http://dx.doi.org/10.22138/2500-0918-2021-18-4-282-294.

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The purpose of this work was to study the characteristics of human papillomaviruses spread in reproductive age patients with low and high degree squamous intraepithelial lesions of the cervix in Yekaterinburg. Material and Methods. In with study 140 female patients of reproductive age with histologically confirmed low and high grade intraepithelial lesions were retrospectively included. HPV-genotyping by polymerase chain reaction was carried out in combination with liquid-based cytology BDSurePath. Formed 4 groups: LSIL, age from 18 to 30 years; LSIL, age from 31 to 44; HSIL, ages 18 to 30; HSIL, ages 31 to 44. Results. Analysis of the obtained data demonstrated that HPV 16 prevails in intraepithelial squamous cell lesions of the cervix of low and high degree in women of reproductive age in Yekaterinburg. In women aged 18-30 years, compared with the older reproductive age (31-44 years), multiple infections with 3, 4 or more HPV genotypes are more often recorded, regardless of the degree of damage. In addition to HPV 16, low-grade lesions in young women are most often associated with HPV 31, 51, and 52, and high-grade lesions with types 31, 33 and 52. HPV 33 is characteristic of a high degree of intraepithelial squamous cell lesions, especially in patients of older reproductive age. With intraepithelial squamous lesions of low and high degree, regardless of age, an equally high concentration of HPV DNA is observed.
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Shin, Sanghyuk S., Catherine L. Carpenter, Maria L. Ekstrand, et al. "Cervical cancer awareness and presence of abnormal cytology among HIV-infected women on antiretroviral therapy in rural Andhra Pradesh, India." International Journal of STD & AIDS 30, no. 6 (2019): 586–95. http://dx.doi.org/10.1177/0956462419825950.

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Cervical cancer is a leading cause of death among women in low- and middle-income countries, and women living with HIV are at high risk for cervical cancer. The objective of this study was to estimate the prevalence and correlates of cervical cancer and pre-cancer lesions and to examine cervical cancer knowledge among women living with HIV receiving antiretroviral therapy in rural Andhra Pradesh, India. We conducted cytology-based screening and administered a standardized questionnaire among 598 HIV-infected women. We found 5 (0.8%), 39 (6.5%), 29 (4.9%), and 4 (0.7%) had atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and squamous cervical carcinoma (SCC), respectively. In multivariable logistic regression analysis, ASCUS/LSIL was independently associated with age >16 years old at first sexual encounter and smokeless tobacco use. We found no factors associated with HSIL/SCC. In total, 101 women (16.9%) had heard of cervical cancer and 28 (27.7%) of them correctly identified HIV infection as a risk factor. In light of the high prevalence of pre-cancer lesions and low level of cervical cancer knowledge in our study population, focused interventions are needed to improve cervical cancer literacy and prevention among rural women living with HIV.
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Valero, Andrés, María Lorena Roldán, María Fernanda Ruiz, Juan Manuel Teijeiro, Susana Beatriz Marquez, and Patricia Estela Marini. "Deleted in Malignant Brain Tumor 1 (DMBT1) Expression Pattern in Normal Cervix and at Different Stages of Squamous Intraepithelial Lesions." Open Biomarkers Journal 8, no. 1 (2018): 1–8. http://dx.doi.org/10.2174/1875318301808010001.

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Background: Cervical cancer is one of the most frequently occurring malignancies in women worldwide, with high mortality rates. Cervical Squamous Cell Carcinoma (SCC) presents previous states of non-invasive precursor lesions, and early stage Low-Grade Squamous Intraepithelial Lesions (LSIL) regress to normal or Atypical Squamous Cells of Undetermined Significance (ASCUS) in approximately 50% of cases. Deleted in Malignant Brain Tumors 1 (DMBT1) is a tumour suppression glycoprotein, which absence is considered a malignancy marker in many epithelial cancers. Objective: To analyse DMBT1’s presence and localization in SCC and precursor lesions. Method: Immunohistochemistry for DMBT1 was performed in cervix biopsies classified as normal, LSIL, HSIL and SCC. Results: DMBT1 was detected at the supranuclear and sometimes infranuclear regions of the endocervix monolayer epithelial cells in normal and HSIL biopsies. In LSIL samples the detection of DMBT1 in endocervix was variable between patients. Also variable was DMBT1 staining in cells of glandular epithelium. The glycoprotein was not detected in the stratified epithelium of the exocervix, regardless of the lesion grade; nor in dysplastic cells. Conclusion: The absence of DMBT1 from endocervix only in some samples of LSIL is promising as a candidate for possible lesion regression potential marker.
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Apiwattanasevee, Warangkana, Nida Jareemit, and Boonlert Viriyapak. "Spontaneous Regression Rate of Low Grade Cervical Intraepithelial Lesions Diagnosed from Colposcopy." Journal of Health Science and Medical Research 36, no. 3 (2018): 233. http://dx.doi.org/10.31584/jhsmr.2018.36.3.16.

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Objective: To evaluate the spontaneous regression rate and its associated factors of low grade intraepithelial lesionsafter colposcopy in Thai women.Material and Methods: A retrospective study of the data of Thai women, not younger than 21 years old with liquidbased cervical cytology of atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL), who had received colposcopic examination with histologically proven cervical intraepithelial neoplasia grade 1 (CIN1) or human papillomavirus (HPV) infection. All patients underwent cytologic tests as the follow-up method for at least 2 years at the Gynecology Clinic, Siriraj Hospital. Analyzed data included patient characteristics, cervical cytological and pathological results, colposcopic findings and evidence of cytological regression. The correlations between each variable and regression status were then measured.Results: Data of a total of 154 patients who completed 2 years of follow-up were reviewed. One hundred and two patients had cytologic regression, showing a regression rate of 66.2%. There was 31.8% persistent abnormal cytology, and 2.0% progressed to high-grade cervical intraepithelial lesions. All patients with persistence or progression of cervical cytology had no invasive lesion. The only factor significantly related to cytologic regression was the pattern of colposcopic findings (p-value=0.041). The HPV-specific lesion on the colposcopy showed the significant pattern with an odds ratio of 3.5 (95% confidence interval=1.2-10.1, p-value=0.028).Conclusion: Women who had initial cervical cytology of ASC-US or LSIL with colposcopic histological confirmation of CIN1 or HPV infection had spontaneous regression, about two-thirds within 2 years of follow-up time. Thus, conservative management in these patients should be considered.
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Phongnarisorn, C., J. Srisomboon, S. Siriaungkul, et al. "Women in a region with high incidence of cervical cancer warrant immediate colposcopy for low-grade squamous intraepithelial lesion on cervical cytology." International Journal of Gynecologic Cancer 16, no. 4 (2006): 1565–68. http://dx.doi.org/10.1136/ijgc-00009577-200607000-00011.

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The objective of this study was to determine the prevalence of high-grade histologic diagnoses in women who had low-grade squamous intraepithelial lesion (LSIL) on Pap smear in an area with high incidence of cervical cancer. We conducted a retrospective study of 220 women with LSIL cytology undergoing colposcopic examination in Chiang Mai University Hospital between January 1999 and July 2004. The histologic diagnoses, obtained from colposcopically directed biopsy or electrical loop excision after initial colposcopy, showed that 80 (36.4%) women had histologically confirmed high-grade lesions and 11 (5%) women had microinvasive (9) and frankly invasive (2) carcinomas. Overall, 41.5% of women with LSIL on Pap smear had significant underlying lesions, requiring appropriate treatment. In conclusion, in the region with high incidence of cervical cancer, women with LSIL cytology are at increased risk of having underlying high-grade lesions and invasive cancer. Immediate referral for colposcopy is warranted.
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Alrajjal, Ahmed, Vaishali Pansare, Moumita Saha Roy Choudhury, Mir Yousufuddin Ali Khan, and Vinod B. Shidham. "Squamous intraepithelial lesions (SIL: LSIL, HSIL, ASCUS, ASC-H, LSIL-H) of Uterine Cervix and Bethesda System." Cytojournal 18 (July 17, 2021): 16. http://dx.doi.org/10.25259/cytojournal_24_2021.

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For every 100,000 women in the United States, eight new cervical cancer cases and two deaths are reported as per the most recent (2017) Center of Disease Control and Prevention statistics. Of all the gynecologic cancers (ovary, uterus, cervix, vagina, and vulva), only cervical cancer has a screening test. Cervical Pap test (or Pap smear) is the best screening method for cervical precancerous lesions and is best reported using a unified and a well-established reporting system like The Bethesda System. In this system, “Epithelial cell abnormality: Squamous” includes squamous intraepithelial lesion (SIL) category which encompasses a spectrum of squamous cell lesions starting from the precancerous lesions of low-grade SIL (LSIL) to high-grade SIL (HSIL), and ultimately invasive squamous cell carcinoma. However, depending on the qualitative and quantitative limitations with the specimen, some equivocal morphological features suggestive of squamous cell abnormality may fall under equivocal category: “Atypical Squamous Cells” (ASCs), which are subdivided into two categories; “Atypical Squamous Cells of Undetermined Significance” (ASC-US) or “Atypical Squamous Cells, HSIL cannot be excluded” (ASC-H), based on the suspected underlying lesion LSIL versus HSIL, respectively. This review provides the key cytologic features that distinguish Bethesda squamous categories from other important entities, using algorithmic approach and illustrations of common cytomorphologic patterns for clear identification of those entities in practice. The important mimickers which may be considered during the differential interpretation of SIL are discussed and presented here in a brief cytomorphologic review.
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Canbey, Ceren, Sena Şen, and Tevhide Bilgen Özcan. "Diagnostic utility of cell block preparations from liquid-based cytology in cervical lesions: A comparative retrospective analysis." Cytojournal 22 (May 6, 2025): 48. https://doi.org/10.25259/cytojournal_3_2025.

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Objective Cervical cancer ranks as the fourth most prevalent cancer among women globally; it originates in the cervix and has a significant association with human papillomavirus (HPV) infection. The purpose of this study was to investigate the diagnostic utility of cell block (CB) preparations from liquid-based cytology samples in identifying cervical lesions among Turkish patients with HPV. This approach was intended to supplement conventional Pap smear tests and HPV testing. Material and Methods A retrospective analysis was conducted on 60 HPV-positive cervical smear samples processed through the ThinPrep Pap test. CBs were prepared from liquid-based residues, stained with hematoxylin and eosin, and analyzed. Cytological diagnoses were compared with histopathological findings from colposcopy-guided biopsies. The relationships between the Pap smear, CB, and biopsy results were statistically analyzed. Results Pap smear cytology identified 1.6%, 16.6%, 43.3%, and 3.3% as high-grade squamous intraepithelial lesion (HSIL), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells of undetermined significance, and atypical squamous cells - HSIL cannot be excluded + LSIL, respectively. The CB evaluations classified 6.6% of the samples as cervical intraepithelial neoplasia (CIN)1, 1.6% as CIN2, and 1.6% as squamous cell carcinoma (SCC), with 78.3% deemed negative. Histopathological biopsy revealed CIN1 in 11.7%, CIN2 in 1.7%, and CIN3 in 8.3% of the patients. High concordance was observed between the Pap smear and CB diagnoses for negative and low-grade lesions, although discrepancies occurred in higher-grade lesions. HPV testing revealed 65% high-risk positivity, predominantly for HPV16 and HPV18. Significant correlations were found among HPV subtype positivity, CB, and biopsy diagnosis (P < 0.05). Conclusion CB preparations provide enhanced diagnostic accuracy for high-grade lesions and SCC, thus complementing Pap smear cytology and HPV testing. This approach supports their integration into the routine cervical cancer screening protocols in Türkiye. Further global, multicenter studies are recommended to validate these findings.
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Jovic, Milena, Dane Nenadic, Zvonko Magic, et al. "Reliability of the CINtecTM p16INK4a immunocytochemical test in screening cervical precancerous lesions." Vojnosanitetski pregled 65, no. 3 (2008): 211–19. http://dx.doi.org/10.2298/vsp0803211j.

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Background/Aim. Overexpression of p16INK4a has been found to be linked with genomic integration of high-risk human papillomavirus (HPV) and the developement of precancerous cervical intraepithelial lesions. The aim of this study was to examine is there a higher positive level of correlation between grade of histological dysplasia and p16INK4a level of expression in cervical smear, compared to results of Papanicolaou test. We also examined the correlation between HPV type, p16INK4a expression and Papanicolau test results. Methods. A total of 48 women with precanceorous cervical lesions and HPV cervicitis and 10 healthy women were enrolled in the study. Papanicolaou test, CINtecTM p16INK4a citological immunohistochemical test, polymerase chain reaction (PCR) HPV 16, 18, 31, 33 analysis and histopathology of the lesion were performed in all the patients. Results. Comparing the results of Papanicoulaou test and the grade of histological dysplasia, low-grade squamous intraepithelial lesion (LSIL) was confirmed in 38%, and high-grade squamous intraepithelial lesion (HSIL) in 69.2% of the patients (p > 0.05). Significant positive correlation was found between p16 overexpression and grade of histological dysplasia (p = 0.000). Overexpression p16 was found in 70% of LSIL and 94.4% of HSIL. Positive correlation was found between p16 overexpression and grade of dysplasia in Papanicolaou test (p = 0.011). In 38% of LSIL and 15% of HSIL cases p16 was not expressed. The most frequently found HPV type in PCR analysis was HPV16. Analysing the results of p16 test according to HPV status and Papanicolaou test rather heterogenous results were obtained. Conclusion. In the patients with precancerous cervical lesions a higher level of correlation was found between the grade of histological dysplasia and p16INK4a level of expression in the cervical smear, compared to the results of Papanicolaou test.
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Dobrokhotova, Yu E., E. I. Borovkova, V. V. Romanovskaya, and I. V. Stepanyants. "Long-term outcomes of cytokine therapy in pregnant women with cervical intraepithelial neoplasia." Russian Journal of Woman and Child Health 5, no. 2 (2022): 106–11. http://dx.doi.org/10.32364/2618-8430-2022-5-2-106-111.

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Aim: to assess long-term outcomes of exogenous cytokine therapy in pregnant women with cervical intraepithelial neoplasia (CIN). Patients and Methods: this prospective study included 50 pregnant women with CIN. Women were randomized into two groups. Group 1 women (n=30, mean age 31.6±1.7 years) received vaginal suppositories with Superlymph 25 U. Group 2 women (n=20, mean age 29.8±1.4 years) received rectal suppositories with Superlymph 25 U. Cervical smear cytology (at baseline, 22 days after starting treatment, and 6 weeks after delivery), colposcopy, and cervical biopsy (at baseline and 6 weeks after delivery) were performed. Results: in group 1, cytology revealed high-grade squamous intraepithelial lesion (HSIL) in 43.3%, atypical squamous cells-cannot exclude a high-grade lesion (ASC-H) in 6.7%, and atypical squamous cells of undetermined significance (ASCUS) in 10%. In group 2, cytology revealed low-grade squamous intraepithelial lesion (LSIL) in 25%, HSIL in 45%, ASC-H in 10%, and ASCUS in 20%. After the treatment course, in group 1, a regress from HSIL to LSIL was detected in 6.7%, regress from LSIL to ASCUS in 3.3%, and regress from HSIL to ASC-H in 3.3%. In group 2, NILM was detected in 5%, a regress from HSIL to LSIL in 5%, and regress from LSIL to ASCUS in 5%. Histologically, LSIL was verified in 50% of women of both groups, CIN grade 2 in 36.7% (group 1) and 40% (group 2), CIN grade 3 in 13.3% (group 1) and 10% (group 2). Six weeks after delivery, cytological abnormalities were identified in 30 women of both groups (HSIL in 56.7% and LSIL in 43.3%). Histology detected carcinoma in situ in 3.3% and CIN grade 2–3 in 53.3%. Delivery in time (on average, at 38.4±1.1 weeks of gestation) occurred in all women. Conclusion: trend toward the improvement of cytological parameters irrespective of the mode of drug administration is reported after finishing cytokine therapy. Normalization of cytological findings was reported in 3.3% (group 1) and 5% (group 2), while improvement was reported in 6.6% (group 1) and 10% (group 2). No worsening was reported.
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Ishida, Katsunari, Makoto Nagasaki, Masayuki Kobayashi, Tatsushi Nakagawa, Toru Nabika, and Kiyomi Taniyama. "Evaluation of the In Situ Hybridization Signal Patterns of Liquid-Based Cytological Human Papillomavirus Specimens for Diagnosing Squamous Intraepithelial Lesion." ISRN Pathology 2011 (August 10, 2011): 1–9. http://dx.doi.org/10.5402/2011/219790.

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To examine the diagnostic utility for squamous intraepithelial lesion (SIL) by cytological in situ hybridization (c-ISH) for the human papillomavirus using liquid-based cytology specimens, we investigated c-ISH signal patterns in the cases of low-grade SIL (LSIL), atypical squamous cells of undetermined significance (ASC-US), and high-grade SIL (HSIL). Episomal (E) and/or integrated (I) signals were observed. Two signal patterns (E≧I or I>E) were obtained by counting the number of E+ or I+ cells. E≧I was specific to LSIL and ASC-US (10/12); I>E, to HSIL (9/11) (P<0.01, χ2 test), suggesting significant utility of c-ISH in diagnosing SIL. In the cell fraction, E≧I in large cells was dominant in LSIL. Two cases of I>E in large cells of LSIL showed HPV persistence and/or progression during follow-up. Thus, c-ISH is useful in routine testing for diagnosing cervical dysplastic lesions, especially for detecting LSIL suspected for progression.
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Saha, Rama, Deepika Pandey, Santosh Kumar Mondal, Tummidi Santosh, Sujaya Mazumder, and Indranil Chakrabarti. "A retrospective study on cervical cancer screening- In a newly opened tertiary care Centre in Eastern India." IP Journal of Diagnostic Pathology and Oncology 8, no. 2 (2023): 83–88. http://dx.doi.org/10.18231/j.jdpo.2023.018.

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: One of the most prevalent cancers, cervical cancer is also the leading cause of mortality for women in underdeveloped nations. A fundamental test for finding infections and precancerous diseases is the Papanicolaou smear. This study aims to comprehend the function of cervical screening in detecting premalignant, malignant, and non-neoplastic lesions as well as the prevalence of different lesions in women who received a traditional pap smear technique. We screened women in the age group of 15-70 years who attended the Outpatient department of the Obstetrics and Gynaecology department of AIIMS, Kalyani. All women who gave consent for screening by Pap smear test were included. Of 2133 cases, most of the cases were benign comprising of Negative for Intraepithelial Lesion or malignancy (NILM) of about 1989 (93.24%) cases, 705 (33.05%) inflammatory. Atypical squamous cells of undetermined significance in 44 cases (2.06%), Atypical squamous cells cannot exclude HSIL in 3 (0.14%), low-grade squamous intraepithelial lesion (LSIL) in 11 (0.52%), high-grade squamous intraepithelial lesion (HSIL) in 5 (0.23%) women and Atypical glandular cell in 7 (0.33%). Out of 202 asymptomatic women (9.47%), 12 cases (0.56%) showed epithelial cell abnormality (8 ASCUS, 2 LSIL, 1 ASCH, 1HSIL) (Odds ratio=0.5056, Significance level, P=0.0362). Conventional Pap smear test is a very easy and cheap diagnostic tool to detect premalignant, malignant, and non-neoplastic lesions and the prevalence of various lesions. As per the American Cancer Society (ACS), a pap smear should start from 25 years to be done till 65 years (repeated after every 3 years).
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Monsrud, A., V. Avadhani, M. Mosunjac, and U. Krishnamurti. "PD-L1 Expression in Anal Intraepithelial Neoplasia Versus. Invasive Squamous Cell Carcinoma." American Journal of Clinical Pathology 154, Supplement_1 (2020): S67. http://dx.doi.org/10.1093/ajcp/aqaa161.146.

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Abstract Introduction/Objective Upregulation of programmed death-ligand 1 (PD-L1), an immunoregulatory protein is associated with adverse outcome in several malignancies. Very few studies have evaluated PD-L1 expression in anal lesions. In this study we compare PD-L1 expression in anal squamous intraepithelial lesions (SIL/AIN) with that in invasive squamous cell carcinoma (ISCC) Methods After IRB approval, formalin-fixed paraffin embedded sections from 84 patients (51 with ISCC and 32 without ISCC), from 2010–2018, were immunostained for PD-L1 (Dako 22C3 monoclonal antibody). These included 15 cases with normal mucosa, 60 cases with low grade squamous intraepithelial lesion (LSIL/AIN 1), 52 cases with high grade intraepithelial lesion (HSIL/AIN2-3), and 51 cases of ISCC. Overall tumor proportion score of > 1% tumor cells with partial or complete membrane staining was interpreted as PD-L1 positive (PD-L1 +). Results PD-L1 was positive in 18/51 (35%) and negative in 33/51 (65%) cases of ISCC. Staining was heterogenous in all PD-L1 positive cases, with invasive foci that were negative to 100% positive. Tumor proportion score ranged from 1% to 50%. No PD-L1 membrane positivity was seen in any of the normal mucosa, LSIL/AIN 1, and HSIL/AIN 2-3. Even in cases of microinvasive or invasive carcinoma, PD-L1 positivity was seen only in the invading malignant cells and not in the overlying or adjacent HSIL. One case showed aberrant nuclear staining in 10% of cells in LSIL and HSIL. About 25% of cases showed non-specific basal granular cytoplasmic staining in normal mucosa, LSIL, and HSIL, that correlated with the presence of melanin. Cases with normal mucosa, LSIL/AIN 1, and HSIL/AIN 2-3, were equally distributed between cases with no invasive carcinoma, PD-L1 positive ISCC, and PD-L1 negative ISCC. Conclusion No PD-L1 positivity (membrane staining) was present in normal mucosa or anal squamous intraepithelial lesion/anal intraepithelial neoplasia in our study. Any nuclear staining or granular cytoplasmic staining should not be interpreted as PD-L1 positivity. PD-L1 was only positive in a subset (35%) of invasive squamous cell carcinoma. The expression of PD-L1 is likely to be associated with an invasive malignant process and is a potential target for therapy with PD-L1 inhibitors.
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Daniilidis, Angelos, John Koutsos, Zinon Oikonomou, Maria Nasioutziki, Katerina Hatziparadisi, and Theocharis Tantanasis. "Cytokines of Cervical Mucosa and Human Papilloma Virus Infection of the Cervix: A Descriptive Study." Acta Cytologica 60, no. 1 (2016): 58–64. http://dx.doi.org/10.1159/000445161.

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Objective: The production of cytokines by various cervical cells can be triggered by antigenic stimuli, including human papilloma virus (HPV) infection. The aim of the present study was to evaluate differences in cytokine levels between various intraepithelial cervical lesions. Study Design: A total of 97 women participated in this descriptive study. Within our study population, 27 subjects presented with high-grade squamous intraepithelial lesions (HSIL), 48 with low-grade squamous intraepithelial lesion (LSIL) and 22 with a normal smear. Colposcopy and directed biopsy were performed as needed. To confirm the presence of HPV, an HPV-DNA test was performed using polymerase chain reaction. Using flow cytometry to ThinPrep cervical samples, we assessed the family of interleukins (ILs), including IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor (TNF)-α and TNF-β and transforming growth factor-β1. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS for Windows; version 20.0). Results: Significantly lower levels of IL-1α, IL-2, IL-4 and TNF-α were detected in cervical samples obtained from the LSIL group when compared to samples obtained from the HSIL group. Conclusion: Significant differences in tissue cytokine levels exist between intraepithelial cervical lesions obtained from patients presenting with HSIL versus LSIL.
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Babović, Adnan, Dženita Ljuca, Gordana Bogdanović, and Lejla Muminhodžić. "Abnormal colposcopic images in patients with preinvasive cervical lesions." Journal of Health Sciences 3, no. 2 (2013): 98–102. http://dx.doi.org/10.17532/jhsci.2013.71.

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Introduction: The objective of the study was to determine frequency and to compare frequency of the abnormal colposcopic images in patients with low and high grade pre-invasive lesions of cervix.Methods: Study includes 259 patients, whom colposcopic and cytological examination of cervix was done. The experimental group of patients consisted of patents with pre-invasive low grade squamousintraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL), and the control group consisted of patients without cervical intraepithelial neoplasia (CIN).Results: In comparison to the total number of satisfactory fi ndings (N=259), pathological findings were registered in N=113 (43.6 %) and abnormal colposcopic fi ndings in N=128 (49.4%). The study did notinclude patients with unsatisfactory fi nding N=22 (8.5%). Abnormal colposcopic image is present most frequently in older patients but there are no statistically important difference between age categories(Pearson Chi-Square 0.47, df -3, p=0.923). Frequency of abnormal colposcopic fi ndings (N=128) is the biggest in pathological cytological (N=113) and HSIL 58 (45.3%), LSIL 36 (28.1%). There is statisticallysignifi cant difference in frequency of abnormal colposcopic images in patients with low-grade in comparison to patients with high-grade pre-invasive cervix lesions (Chi-Square test, Pearson Chi-Square 117.14,df-12 p<0.0001).Conclusion: Thanks to characteristic colposcopic images, abnormal epithelium is successfully recognized, but the severity grade of intraepithelial lesion cannot be determined.
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Santos, André Luis Ferreira, Sophie Françoise Mauricette Derchain, Marcos Roberto Martins, Luís Otávio Zanatta Sarian, Edson Zangiacome Martinez, and Kari Juhani Syrjänen. "Human papillomavirus viral load in predicting high-grade CIN in women with cervical smears showing only atypical squamous cells or low-grade squamous intraepithelial lesion." Sao Paulo Medical Journal 121, no. 6 (2003): 238–43. http://dx.doi.org/10.1590/s1516-31802003000600004.

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CONTEXT: Human papillomavirus (HPV) viral load may have an important role in predicting high-grade cervical intraepithelial neoplasia (CIN) in women with cervical smears showing atypical squamous cells or LSIL. OBJECTIVE: To determine whether the assessment of the viral load of high-risk HPV DNA is useful in predicting the detection of high-grade cervical intraepithelial neoplasia (CIN2 and 3) in women referred because of cervical smears showing only atypical squamous cells or LSIL. TYPE OF STUDY: Cross-sectional SETTING: Colposcopy Clinic in a University hospital. METHODS: A series of 119 women referred because of atypical squamous cells or LSIL between August 2000 and April 2001 were included. All women were subjected to a new cervical smear, HPV testing for the high-risk types using hybrid capture II (HCII), viral load measurement in relative light units (RLU) and colposcopy, with cervical biopsies (n = 97). Cervical lesions were graded using the CIN classification. RESULTS: Cervical biopsies revealed CIN2 or CIN3 in 11% of the cases, equally among women referred because of atypical squamous cells or LSIL. The HCII test was positive in 16% of women with atypical squamous cells and 52% of those with LSIL (OR = 5.8; 95% CI 1.4 to 26.7). There was strong correlation between CIN2 or CIN3 and positivity for HPV DNA when this group was compared with women with only CIN1 or normal cervix (OR = 7.8; 95% CI 1.5 to 53.4). In ROC analysis for HCII in diagnosing CIN2 and CIN3, the area under the ROC curve was 0.784, and the viral load cutoff point of 10.0 RLU/cutoff presented 77% sensitivity and 73% specificity. Second cytology showing at least atypical squamous cells did not accurately detect CIN2 or CIN3 (OR = 6.4; 95% CI 1.0 to 50.9). The sensitivities of the second cervical smear and HCII were similar, although the specificity of HCII was significantly higher than the second cervical smear. CONCLUSIONS: The viral load of high-risk HPV types was significantly associated with the diagnosis of CIN2 or CIN3 in women referred because of atypical squamous cells and LSIL abnormalities in their cervical smear.
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Sasivimolrattana, Thanayod, Aileen Gunawan, Warattaya Wattanathavorn, et al. "Upregulation of HPV16E1 and E7 expression and FOXO3a mRNA downregulation in high-grade cervical neoplasia." PeerJ 12 (December 6, 2024): e18601. https://doi.org/10.7717/peerj.18601.

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Background Cervical cancer remains a significant global health concern, ranking as the fourth most prevalent cancer among women worldwide. Human papillomaviruses (HPV) transcribe many genes that might be responsible for cervical cancer development. This study aims to investigate the correlation between the expression of HPV16 early genes and the mRNA expression of human FOXO3a, a tumor suppressor gene, in association with various stages of cervical precancerous lesions. Methods Eighty-five positive HPV16 DNA cervical swab samples were recruited and categorized based on cytology stages, i.e., negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cell cannot exclude HSIL (ASC-H), high-grade squamous intraepithelial lesion (HSIL). RT-qPCR was performed to amplify HPV16E1, E4, E6, E6*I, E7, and human FOXO3a mRNA expression in all samples. The relative expression of those genes was calculated using GAPDH as a control. Detection of FOXO3a mRNA expression in the cervical cancer cell line by RT-qPCR and meta-analysis of FOXO3a expression using the RNA-Seq dataset by GEPIA2 were analyzed to support the conclusions. Results Among the cervical samples, HPV16E1 and E7 were significantly increased expression correlating to disease severity. HPV16E4 mRNA expression was 100% detected in all LSIL samples, with a significant increase observed from normal to LSIL stages. Conversely, FOXO3a mRNA expression decreased with disease severity, and the lowest expression was observed in HSIL/squamous cell carcinoma (SCC) samples. In addition, similar results of FOXO3a downregulation were also found in the cervical cancer cell line and RNA-Seq dataset of cervical cancer samples. Conclusion HPV16 early mRNA levels, including E1 and E7, increase during cancer progression, and downregulation of FOXO3a mRNA is a characteristic of cervical cancer cells and HSIL/SCC. Additionally, HPV16E4 mRNA expression was consistently detected in all LSIL samples, suggesting the presence of active viral replication. These findings might lead to further investigation into the interplay between HPV gene expression and host cell factors for targeted therapeutic strategies in cervical cancer management.
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Renshaw, Andrew A., Dina R. Mody, Patricia Styer, Mary Schwartz, Barbara Ducatman, and Terence J. Colgan. "Papanicolaou Tests With Mixed High-Grade and Low-Grade Squamous Intraepithelial Lesion Features: Distinct Performance in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytopathology." Archives of Pathology & Laboratory Medicine 130, no. 4 (2006): 456–59. http://dx.doi.org/10.5858/2006-130-456-ptwmha.

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Abstract Context.—Previous studies have shown that in gynecologic cytology, cases of low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) perform differently on interpretive review. The performance of cases with mixed LSIL and HSIL features is unknown. Objective.—To compare the performance of gynecologic cytology cases of “pure” LSIL and HSIL with cases showing mixed LSIL and HSIL features. Design.—We compiled performance data from the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytopathology from the years 2003 and 2004, and compared the performance of slides showing relatively pure LSIL and HSIL (≤10% misclassification as HSIL and LSIL, respectively) with slides showing mixed LSIL or HSIL features (cases misclassified as LSIL or HSIL >10% of the time). Results.—Interpretations from a total of 4508 cases (2452 HSIL and 2056 LSIL) were analyzed. Overall, the sensitivity of participants on slides with a reference diagnosis of HSIL was 97.3%, and of LSIL was 95.9%. Performance trends for pure versus mixed cases varied by slide type and reference diagnosis. For conventional slides, participant sensitivity on pure HSIL cases was greatest (98.0%) and on pure LSIL cases was least (95.2%), while participant performance on cases with mixed features was intermediate (97.0% for mixed HSIL and 96.7% for mixed LSIL). In contrast, participant performance on ThinPrep slides showed the greatest sensitivity for mixed LSIL slides (97.9%), while performance on mixed HSIL slides showed the lowest sensitivity (95.7%); slides with pure features had intermediate sensitivity levels (96.3% for both HSIL and LSIL). Further evaluation demonstrated that conventional pure HSIL slides performed significantly better than mixed HSIL slides (P = .006), whereas mixed LSIL slides performed better than pure LSIL slides (P = .01). For ThinPrep slides, pure HSIL cases performed similarly to mixed HSIL cases (P = .43), while mixed LSIL cases performed better than pure LSIL cases (P = .04). Conclusion.—Slides with mixed LSIL and HSIL features have measurably distinct performance characteristics in comparison to slides with pure LSIL or HSIL features. Participant performance on conventional mixed cases is distinctly different from performance on ThinPrep mixed cases.
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Jayaprakash, Megha, Sreenija Menon, Georgy Joy Eralil, Alok K. P., and Rajany Jose. "Cervical cytology profile by Papanicolaou smear in a rural setting in mid-Kerala." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 9, no. 10 (2020): 4000. http://dx.doi.org/10.18203/2320-1770.ijrcog20204006.

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Background: With no systematic national screening programme, the rates of cervical epithelial cell abnormalities as reported by various studies range from 1.32% to 25% in India. Majority are epithelial squamous cell abnormalities that include atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL). Worldwide incidence of adenocarcinoma and its precursors have increased over past few decades. Objectives were to study the clinical and cervical cytological profile among women attending camps in rural areas of Thrissur district of Kerala.Methods: A cross sectional study was conducted in 214 women in the 25-65 years age group who attended cancer screening camps in rural areas of Thrissur district. Papanicolaou (Pap) smear was done using standard technique and reported using latest Bethesda classification. Pap smear results were considered as abnormal when the report was ASCUS, atypical glandular cells of undetermined significance, LSIL, high grade squamous intraepithelial lesion or invasive lesion.Results: Of all the smears, 41.6% were negative for intraepithelial lesion or malignancy. Inflammatory smears (nonspecific and specific infection associated) were seen in 57%. Glandular cell abnormality was found in 1.4% and these women were in 31-50 years age group. Among patients with glandular cell abnormality most common symptom was discharge per vaginum.Conclusions: The results of this study may be a pointer to an increase in glandular cytological abnormalities in our population and needs further large-scale studies to confirm. Current screening methods of Pap smear alone may not be adequate to pick up these lesions.
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Matsumoto, Koji, Hiroo Maeda, Akinori Oki, et al. "HLA Class II DRB1*1302 Allele Protects Against Progression to Cervical Intraepithelial Neoplasia Grade 3: A Multicenter Prospective Cohort Study." International Journal of Gynecologic Cancer 22, no. 3 (2012): 471–78. http://dx.doi.org/10.1097/igc.0b013e3182439500.

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ObjectiveGenetic variations in human leukocyte antigens (HLA) class II regions may influence the risk of cervical cancer by altering the efficiency of the immune responses to human papillomavirus antigens. This prospective study was designed to evaluate the effects of HLA class II alleles on the natural course of cervical precursor lesions.MethodsWe followed a total of 454 Japanese women with cytological low-grade squamous intraepithelial lesion (LSIL) and histological cervical intraepithelial neoplasia grades 1 to 2 (CIN1-CIN2). Patients were tested for HLA class II alleles and cervical human papillomavirus DNA at the time of entry and then monitored by cytology and colposcopy every 4 months for a mean follow-up of 39.0 months. We analyzed cumulative probabilities of cytological regression to at least 2 consecutive negative Papanicolaou tests and histological progression to biopsy-positive CIN3.ResultsDuring the follow-up period, 39 lesions progressed to CIN3, and 282 lesions regressed to normal cytology. Progression to CIN3 did not occur in DRB1*1302-positive women, and this protective effect of DRB1*1302 was statistically significant (P = 0.03). Low-grade squamous intraepithelial lesion regressed to normal cytology more quickly in DRB1*1302-positive women than in DRB1*1302-negative women (median time, 8.9 months vs 14.2 months), although the difference was not statistically significant (P = 0.16). The risk of LSIL persistence or progression to CIN3 within 5 years was not affected by any other HLA class II alleles.ConclusionBy using a prospective study design, we demonstrated the protective effect of the DRB1*1302 allele against progression to CIN3 among Japanese women with LSIL.
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Cong, Qing, Yu Song, Qing Wang, et al. "A Large Retrospective Study of 12714 Cases of LEEP Conization Focusing on Cervical Cancer That Colposcopy-Directed Biopsy Failed to Detect." BioMed Research International 2018 (2018): 1–6. http://dx.doi.org/10.1155/2018/5138232.

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Punch biopsy is important in the diagnosis of cervical cancer. However, it may fail to detect early cervical cancers. A retrospective study was performed in the largest academic women’s hospital in China to demonstrate cervical cancer that colposcopy-directed biopsy failed to detect. Methods. Patients who were diagnosed with high-grade squamous intraepithelial lesion (HSIL), adenocarcinoma in situ (AIS), and persistent low-grade squamous intraepithelial lesion (LSIL) via colposcopy-directed biopsy and had further undergone loop electrosurgical excision procedure (LEEP) conization were included. These procedures were performed at Obstetrics and Gynecology Hospital of Fudan University from July 1, 2013, to December 31, 2016. In total, 5.98% (760/12714) of patients who underwent conization were diagnosed with invasive cervical cancer. Persistent LSIL (0.24%), HSIL (6.37%), and AIS (24.31%) were detected cancer by conization. Histological subtypes included squamous cell carcinoma (92.0%), adenocarcinoma (5.1%), adenosquamous carcinoma (1.8%), adenoid basal type carcinoma (0.9%), and small cell neuroendocrine carcinoma (0.1%). Cytology reports consisted of HSIL (45.4%), atypical squamous cells of undetermined significance (ASC-US) (16.1%), and LSIL (11.6%), and atypical squamous cells cannot exclude HSIL (ASC-H) (9.3%), squamous cell carcinoma (0.9%), AGC (atypical glandular cells, 0.9%), AIS (0.4%), and NILM (negative for intraepithelial lesion or malignancy, 15.4%). The sensitivity of high-risk human papillomavirus (hrHPV) screening (96.4%) was significantly higher than that of cytology (84.6%) (P<0.01), with sensitivity of cotesting at 99.8% and a ratio of double-negative results at 0.2%. The sensitivity of cytology and hrHPV screening of different cervical cancer histologic subtypes was also demonstrated. In this large retrospective study, we systematically reported the cytology, hrHPV, pathology, and stages of cervical cancer that colposcopy-directed biopsy failed to detect.
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Mureşan, Daniel, Ioana Cristina Rotar, Silvana Apostol, Georgiana Coroiu, and Florin Stamatian. "HPV IMMUNOHISTOCHEMICAL TESTING AND CERVICAL DYSPLASIA." Medicine and Pharmacy Reports 89, no. 2 (2016): 236–40. http://dx.doi.org/10.15386/cjmed-653.

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Background and aim. HPV (Human Papilloma Virus) infection represents a necessary condition for cervical carcinogenesis. The purpose of this study was to evaluate the efficiency of HPV testing using an immunohistochemical staining kit with implications upon both diagnosis and treatment of cervical intraepithelial neoplasia (CIN).Methods. Seventy-nine patients and eighty-six controls were enrolled in the study. Each patient had completed a physical examination, gynecological examination with cervical sampling using a liquid-based cytology system and also colposcopy. The cervical samples were analyzed according to Bethesda terminology and HPV-HR immunohistochemical staining was performed. In all the patients with high-grade lesion a surgical excision procedure was performed followed by pathological examination of the specimen. The collected data were analyzed using statistical software.Results. The colposcopic examination has detected acetowhite modifications of the cervical epithelium in 47% of patients with ASC-US (Atypical squamous cells of undetermined significance) in 71% of patients with LSIL (Low grade squamous intraepithelial lesion) and in 100% of patients with HSIL ( High grade squamous intraepithelial lesion). The biopsy confirmed the diagnosis of LSIL in 27% of biopsy specimens in patients with ASC-US and in 79.99% of patients with LSIL respectively. In all patients with HSIL the diagnosis was CIN II or higher. The percentage of HPV-HR (Human Papilloma Virus – High Risk) positivity porportionaly increased with the severity of cytological diagnosis: 30% in ASC-US, 42.86% in LSIL and 75% in HSIL patients. The sensitivity of detection of HPV-HR was 50% with CI 95% [17.45;82.55] for ASC-US, 77.77% with CI 95% [51.91;92.62] for LSIL and 81.81% with CI 95% [58.99;94.00] for HSIL.Conclusion. HPV testing can be an important screening tool for cervical dysplasia. The HPV testing targeting high risk types is indicated for ASC-US and LSIL triage. The present work sustains the idea of introducing HPV testing as a primary screening tool for cervical cancer.
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Coloma, F., M. Mu??oz, J. Terr??dez, et al. "Spontaneous evolution of low-grade squamous intraepithelial lesions (LSIL)." Journal of Lower Genital Tract Disease 11, no. 3 (2007): 197. http://dx.doi.org/10.1097/01.lgt.0000265780.82538.50.

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Wang, P. H., and J. L. Ko. "Implication of human telomerase reverse transcriptase in cervical carcinogenesis and cancer recurrence." International Journal of Gynecologic Cancer 16, no. 5 (2006): 1873–79. http://dx.doi.org/10.1136/ijgc-00009577-200609000-00023.

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The objective of this study was to evaluate the implication of human telomerase reverse transcriptase (hTERT) in cervical carcinogenesis and cancer recurrence. One hundred three cases of uterine cervix, including 20 normal, 13 low-grade squamous intraepithelial lesion (LSIL), 30 high-grade squamous intraepithelial lesion (HSIL), and 40 squamous cell carcinoma (SCC) tissues, were evaluated for hTERT immunoreactivity. The expressions of hTERT in normal, LSIL, HSIL, and SCC tissues were compared by Fisher exact or Chi-square test. The relationships between hTERT and clinicopathologic variables of SCC were also assessed. Furthermore, SCC patients were subdivided into negative and positive hTERT expression subgroups, and Kaplan–Meier curves were used to plot the cumulative recurrence hazard for 5 years. There was a significant difference for hTERT expression between LSIL and HSIL subgroups (P< 0.001) but no significant difference between normal and LSIL as well as HSIL and SCC subgroups. For SCC patients, hTERT expression was positive in lymph nodes, vagina, and parametrium metastastic cases. However, it did not reach a significant difference. The cumulative recurrence hazard for 5 years was about 29% in positive hTERT expression subgroup compared to 0% in negative hTERT subgroup (P= 0.2866). In conclusion, a point stage of HSIL exists in the progression of cervical carcinogenesis when the hTERT expression increases significantly. Moreover, SCC patients with positive hTERT expression may have higher cumulative recurrence hazard.
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Sakdadech, Nawin, Tanarat Muangmool, and Jatupol Srisomboon. "HIV-Infected Women with Low-Grade Squamous Intraepithelial Lesion on Cervical Cytology Have Higher Risk of Underlying High-Grade Cervical Intraepithelial Neoplasia." International Journal of Environmental Research and Public Health 18, no. 19 (2021): 10211. http://dx.doi.org/10.3390/ijerph181910211.

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Objective: To evaluate the risk of histological high-grade cervical lesions defined as cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with human immunodeficiency virus (HIV) infection who had low-grade squamous intraepithelial lesions (LSIL) on cervical cytological screening compared with HIV-uninfected women who had similar cytology. Methods: 127 HIV-positive women aged 18–65 years with LSIL cytology undergoing colposcopic examination between January 2008 and December 2019 at Chiang Mai University Hospital were reviewed. By matching 1:1 ratio for age (±5 years) and examination time period (±12 months), 127 HIV-negative women with LSIL cytology in the same period were recruited as controlled subjects for comparison. The patients’ characteristics, HIV status, CD4 counts, antiretroviral therapy, and histopathology on cervical biopsy were analyzed. Results: HIV-infected women significantly had early sexual debut (age < 20 years) and more sexual partners (≥2) than HIV-uninfected women. The risk of underlying CIN2+ in HIV-infected women was significantly higher than that in HIV-negative women (20.5% vs. 9.4%, p = 0.021) with an odds ratio (OR) of 2.47 and 95% confidence interval (CI) = 1.18–5.14. After adjustment, the risk of underlying CIN2+ in HIV-infected women remained significantly higher than that in HIV-uninfected women (adjusted OR = 2.55, 95% CI = 1.11–5.82, p = 0.027). Conclusion: Among women with LSIL on cervical cytology, the risk of underlying CIN2+ in HIV-infected women was approximately 2.5 times higher than those without HIV infection. Colposcopy is indicated particularly in the case of women with a long duration of HIV infection.
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48

Chen, C. A., C. Y. Liu, H. H. Chou, et al. "The distribution and differential risks of human papillomavirus genotypes in cervical preinvasive lesions: a Taiwan Cooperative Oncologic Group Study." International Journal of Gynecologic Cancer 16, no. 5 (2006): 1801–8. http://dx.doi.org/10.1136/ijgc-00009577-200609000-00013.

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To clarify the distribution and relative risk of different human papillomavirus (HPV) genotypes in cervical preinvasive lesions, 1246 women with abnormal Papanicolaou smear including atypical squamous cell of unknown significance (ASCUS), atypical glandular cell of unknown significance (AGUS), low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL) were enrolled in a multicenter, cross-sectional study. Colposcopy and HPV tests with hybrid capture 2 and polymerase chain reaction–reverse line blot were performed. The prevalences of HPV in ASCUS/AGUS-negative histology, ASCUS/AGUS, LSIL, HSIL, and invasive cancer were 33.8%, 38.3%, 74.9%, 84.3% and 100%, respectively, with an overall positive rate of 68.8%. The most common HPV types were HPV 16 (18.5%), 52 (16.5%), 58 (13.2%), 33, 51, 53, 18, 39, 59, 66, MM8, and 31. In comparing the relative risk of HPV infection in different disease status, LSIL and HSIL/carcinoma had a 4.64 (95% CI: 2.98–7.24) and 10.53 (95% CI: 6.69–16.58) folds of risk of high-risk HPV infection than the negative group. The same was true in mixed HPV infection, but not in low-risk type infection. Looking into each high-risk HPV type, the relative infection risks for LSIL and HSIL/carcinoma, in comparison with the negative group, were 1.67 (0.63–4.43) and 8.67 (3.46–21.70), 2017 (1.01–4.68) and 3.04 (1.42–6.47), and 1.40 (0.52–3.77) and 5.22 (2.07–13.19) for HPV type 16, 52 and 58, respectively. The study confirmed the high prevalence and risky nature of HPV 52 and 58 in Taiwanese population and conveyed the need to include these HPV types in vaccine development.
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49

Schiffman, Mark, and Diane Solomon. "Findings to Date From the ASCUS-LSIL Triage Study (ALTS)." Archives of Pathology & Laboratory Medicine 127, no. 8 (2003): 946–49. http://dx.doi.org/10.5858/2003-127-946-ftdfta.

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Abstract Controversy exists in the United States regarding the proper evaluation and management of low-grade squamous intraepithelial lesion (LSIL) and equivocal (atypical squamous cells of undetermined significance [ASCUS, now ASC-US]) cervical cytologic interpretations. To address this issue, the National Cancer Institute initiated the ASCUS-LSIL Triage Study (ALTS). ALTS is a multicenter, randomized clinical trial designed to evaluate 3 alternative methods of management, namely, immediate colposcopy, cytologic follow-up, and triage by human papillomavirus (HPV) DNA testing. This article summarizes the major findings of ALTS that have been published to date. Patients with ASCUS (n = 3488) or LSIL (n = 1572) were randomly assigned to research arms between November 1996 and December 1998, and were monitored for 2 years. The disease outcome was histologic cervical intraepithelial neoplasia (CIN) 3/cancer. The prevalence of oncogenic HPV was too high to permit effective triage of LSIL using HPV DNA testing by Hybrid Capture 2. However, for the women referred with a cytologic interpretation of ASCUS, HPV triage proved useful, with sensitivity equivalent to immediate colposcopy and a halving of colposcopic referrals. Among older women with ASCUS, HPV testing remained sensitive for detecting CIN 3 and cancer, but the referral percentage was dramatically lower compared to younger women. ALTS yielded insight into the performance of cytology and histopathology; experienced pathologists differed significantly in their interpretations of cervical abnormalities, especially histologic CIN 1 and cytologic ASCUS. Nonetheless, it was possible to distinguish a relatively uncommon type of ASCUS, equivocal for high-grade squamous intraepithelial lesion, that has a high positive predictive value for identifying women with underlying high-grade CIN. Many additional analyses are underway.
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50

Corrêa, Flávia de Miranda, Fábio Bastos Russomano, and Caroline Alves de Oliveira. "Colposcopic triage methods for detecting cervical intraepithelial neoplasia grade 3 after cytopathological diagnosis of low-grade squamous intraepithelial lesion: a systematic review on diagnostic tests." Sao Paulo Medical Journal 130, no. 1 (2012): 44–52. http://dx.doi.org/10.1590/s1516-31802012000100008.

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CONTEXT AND OBJECTIVE: The age-stratified performance of the oncogenic HPV-DNA (human papillomavirus deoxyribonucleic acid) test for triage of low-grade squamous intraepithelial lesions (LSIL) requires investigation. The objective of this study was to evaluate and compare the age-stratified performance (cutoff point: 35 years) of oncogenic HPV-DNA testing and repeated cytological tests, for detecting cervical intraepithelial neoplasia grade 3 (CIN3), in order to triage for LSIL. DESIGN AND SETTING: Systematic review. Studies were identified in nine electronic databases and in the reference lists of the articles retrieved. METHODS: The eligibility criteria consisted of initial cytological findings of LSIL; subsequent oncogenic HPV-DNA testing and repeated cytological tests; and CIN3 detection. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) guidelines were used for quality assessment. Qualitative information synthesis was performed. RESULTS: Out of 7,776 studies, 284 were identified as pertinent and three fulfilled the eligibility criteria. The CIN3 prevalence ranged from 6% to 12%. The HPV-DNA positivity rate ranged from 64% to 83%; sensitivity for CIN3 detection ranged from 95.2% to 100%; and specificity was available in two studies (27% and 52%). The sensitivity of repeated cytological tests, in relation to the threshold for atypical squamous cells of undetermined significance (ASCUS), was available in two studies (33% and 90.8%); and specificity was available in one study (53%). CONCLUSIONS: Currently, there is no scientific evidence available that would prove that colposcopic triage using oncogenic HPV-DNA testing to detect CIN3 performs better than repeated cytological tests, among women with LSIL aged 35 years and over.
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