High-grade Squamous Intraepithelial Lesion Cytology Research Articles

Conservative management of cervical intraepithelial neoplasia 2 and prediction of its progression - a retrospective study.

Cervical intraepithelial neoplasia 2 (CIN2) evolution is controversial, and some of them regress spontaneously in a two-year follow-up. The purpose of this work was to evaluate the percentage of CIN2 progression or persistence during a 24-month follow-up, using clinical predictors such as human papillomavirus (HPV) genotype and cytology results. This is a retrospective case-control study and included patients of reproductive age who had a new diagnosis of CIN2 who were monitored for lesion regression (Group 1, n=72 patients), and progression or persistence (Group 2, n=36 patients). A multinominal logistic regression was preferred to evaluate the impact that various categorical risk elements can lead to outcomes of persistence or progression of CIN2. We also performed a linear regression to assess the risk of CIN2 progression or persistence using the interaction between clinical predictors. A previous cervical cytology indicative of high-grade squamous intraepithelial lesion (HSIL) [relative risk ratio (RRR): 3.85, 95% confidence interval (CI): 1.66-8.90] or atypical squamous cells, cannot exclude HSIL (ASC-H) can highly raise the probability of a CIN2 progression or persistence. The presence of HPV16 increased the risk of CIN2+ with 3.77 (95% CI: 0.78-5.00), the presence of HPV18 increased the probability of CIN2+ with 4.39 (95% CI: 1.35-14.33), and other high-risk HPV (HR-HPV) strains increased the probability of CIN2+ with 3.62. The highest risk issue was produced by the interaction between HSIL* HPV16, ASC-H* HPV16, and ASC-H* HPV18. When discussing follow-up for CIN2 lesions, it is important to offer careful consideration and monitoring of patients with a previous HSIL or ASC-H cytology, with or without HPV 16, 18 or other HR-HPV strains, as their presence significantly increased the risk of CIN2 progression and persistence.

Recurrent High-Grade Squamous Intraepithelial Lesion After Loop Excision Procedure Versus Loop Procedure With Top Hat.

To evaluate single-pass loop electrosurgical excision procedure (LEEP-SP) versus LEEP with top hat (LEEP-TH) in terms of treatment failure defined as high-grade squamous intraepithelial lesion (HSIL) cytology within 2 years' follow-up. This single-institution cohort study used a prospectively collected cervical dysplasia database including all patients who underwent LEEP-SP or LEEP-TH for biopsy-proven cervical intraepithelial neoplasia between 2005 and 2019. Of 340 patients included, 178 underwent LEEP-SP and 162 LEEP-TH. The LEEP-TH patients were more likely to be older (mean age, 40.4 vs 36.5 years; p < .001) and have a positive preprocedure endocervical sampling (68.5% vs 11.8%; p < .001). Positive margins were found in 23 LEEP-SP (12.9%) and in 25 LEEP-TH (15.4%; p = .507). There was no significant difference in depth of excision between LEEP-SP (13.21 ± 23.19 mm) and LEEP-TH (17.37 ± 28.26 mm; p = .138). At 2 years, there was no difference in the rates of HSIL cytology (5.2% vs 6.3%; p = .698), any positive human papillomavirus test, or HSIL cytology (25% vs 15%; p = .284). The 57 patients undergoing repeat excision were more likely to be older (mean age, 40.95 vs 37.52 years; p = .023), have had a LEEP-TH (26.3% vs 73.7%; p < .001), and have initial cytologic HSIL (64.9% vs 35.0%; p < .001). In this single-institution study, there is no difference in the rate of recurrent HSIL in patients undergoing LEEP-SP versus LEEP-TH. A LEEP-TH may have limited additional benefit over a LEEP-SP in the treatment of cervical HSIL.

Accelerating Cervical Cancer Screening With Human Papillomavirus Genotyping

Selective utilization of human papillomavirus (HPV) genotyping in cervical cancer screening can accelerate clinical management, leading to earlier identification and treatment of precancerous lesions and cancer. Specifically, immediate colposcopy (instead of 1-year return) is recommended in persons with normal cytology and HPV genotypes 16 and/or 18, and expedited treatment (instead of colposcopy) is recommended in persons with high-grade squamous intraepithelial lesion (HSIL) cytology and HPV genotype 16. The effects of implementing HPV testing and genotyping into a screening program are largely unknown. Average-risk persons aged 30-65 years screened for cervical cancer in the National Breast and Cervical Cancer Early Detection Program from 2019 to 2020 were included (N=104,991). Percentage HPV genotyping test positivity was estimated within cytology result categories. Analyses were performed in 2022. The most common abnormality was positive high-risk HPV testing with normal cytology, representing 40.1% (7,155/17,832) of all abnormal test result categories; HSIL cytology represented 3.0% (530/17,832) of all abnormal test result categories. In high-risk HPV‒positive persons with normal or high-grade cytology, HPV genotyping could accelerate management (immediate colposcopy and expedited treatment) in 5.4% of all persons with abnormal screening test results; if HPV genotyping had been performed in all high-risk HPV‒positive persons with normal or HSIL cytology, approximately 13.1% could have accelerated management. HPV genotyping in human papillomavirus‒positive persons with normal or HSIL cytology could accelerate management in a sizable percentage of persons with abnormal test results and may be particularly useful in populations with challenges adhering to longitudinal follow-up.

Screen-and-treat approach in managing cervical cancer precursor lesions: An observational study with 524 women

ObjectiveTo detect factors related to overtreatment with the “Screen-and-treat” approach (S&T) in women with suspicious cervical precancerous lesions. Study designA retrospective observational study of 524 women with high-grade squamous intraepithelial lesions (HSIL) or more severe (HSIL+) in cytology, treated by the Large Loop Excision of the Transformation Zone (LLETZ): 161 without a previous biopsy (S&T group) and 363 with a previous biopsy (biopsy group) from January 2017 to July 2020. The main outcome was a diagnosis of LLETZ: negative (negative or low-grade squamous intraepithlelial lesion LSIL) or HSIL+. A negative diagnosis was interpreted as “overtreatment.” Results were analyzed as a function of the S&T approach (whether previous biopsy or not). Variables were obtained from medical records, and were compared with Chi-square or Fisher's exact test (p, p-value), to estimate the chances of a logistic regression analysis (Odds Ratio, OR, or admitting a Confidence Interval (CI) of 95 %). ResultsNo differences were observed in groups regarding menopausal status, smoking, hormonal contraceptive use, colposcopy findings, LLETZ diagnosis, and recurrence. Comparing biopsy vs S&T groups, the frequency of women over 40 years was 28.4 % vs 39.7 % (p = 0.011), and transformation zone type 3 was 12.2 vs 26.8 % (p < 0.001), respectively. In women managed by S&T, when compared to a LLETZ diagnosis, an HSIL+ result was more frequent in women presenting with TZ 1 (93.1 % TZ1 vs 78.5 % TZ2 vs 73.8 % TZ3, p = 0.008) and in women with abnormal colposcopy (92.9 % abnormal vs 38.1 % negative, p < 0.001). Multiple regression analysis found that women with negative colposcopic findings presented a higher risk for negative LLETZ diagnosis (LSIL/Negative final histology) (18.6; 6.18–56.02). ConclusionsNo difference was observed in the LLETZ diagnosis in women who did or did not use the S&T approach: it was adequate for women referred by cytological HSIL along with high-grade colposcopic findings.

Strategic Significance of Low Viral Load of Human Papillomavirus in Uterine Cervical Cytology Specimens.

Infection with high-risk (HR) Human Papillomavirus (HPV) is associated with the development of precancerous lesions or invasive carcinoma of the uterine cervix. Thus, the high viral load (VL) of HR-HPV DNA currently serves as a representative quantitative marker for cervical cancer. However, the clinical significance of low HPV DNA VL remains undetermined. This study aimed to evaluate the clinical association between the low HPV DNA VL and cytology/histologic diagnosis of cervical samples. We searched the electronic medical databases for the resultant analyses of HPV genotyping among patients who underwent treatment for any cervical lesion or who had undergone gynecological examinations with any positive HPV results according to the national cancer screening service between 2015 and 2016. HPV testing with genotyping and semi-quantitative VL measurement was conducted using an AnyplexTM II H28 Detection assay (H28 assay, Seegene, Seoul, Republic of Korea). The H28 assay is a multiplex semi-quantitative real-time PCR test using the tagging of oligonucleotide cleavage and extension (TOCE) technology. The VL was semi-quantified as high (3+; positive signal before 31 PCR cycles), intermediate (2+; positive between 31 and 39 PCR cycles), or low (1+; positive after 40 PCR cycles). Out of 5940 HPV VL analyses, 356 assays (5.99%) were reported as low VL (1+) of HPV DNA. Matched cytology diagnoses were mostly negative findings (n = 347, 97.5%), except for seven cases of atypical squamous cells of undetermined significance (1.9%) and two cases of atypical glandular cells (0.6%). During the follow-up periods, abnormal cytologic diagnoses were identified, including one case of high-grade squamous intraepithelial lesion (HSIL) and two low-grade squamous intraepithelial lesions (LSILs). The matched, confirmative histologic diagnosis of HSIL cytology was compatible with chronic inflammation, wherein the two LSILs had regular check-ups. None revealed clinically concerned outcomes associated with HPV-related squamous lesions. The cytology was most likely negative for malignancy when the VL of HPV DNA was low (1+). Additional strategic monitoring and management may thus be unnecessary.

Safety of Conservative Management of High-Grade Squamous Intraepithelial Lesion in Women Under 30 Years Old.

Objectives:To evaluate the outcomes of conservative management in young women with high-grade squamous intraepithelial lesion (HSIL).Methods:A retrospective cohort study included women younger than 30 years referred with HSIL (cytology or biopsy) managed conservatively from 2012 to 2019, in Campinas/Brazil. Regression was the outcome when no evidence of HSIL was observed in at least two consecutive follow-ups. Kaplan–Meyer method was used to determine regression probabilities. Other tests were chi-square or Fisher, Mann–Whitney and COX regression.Results:During the study period, 89 patients were included. No progression to microinvasive or invasive cancer was observed. Sixty-one (69%) patients were younger than 25 years, and 28 (31%) were aged 25–30 years. Spontaneous regression was seen in 64 (72%) and persistence in 25 (28%) of the overall sample. The average time to regression was 15.4 months (standard deviation [SD] = 7.7), and the follow-up time was 31.6 months (SD 19.0). Age, parity, first sexual intercourse, smoking, hormonal contraception, and colposcopy impression were not different among women with regression or persistence. Regression probabilities were, respectively, 28.9%, 60.2%, and 78.1% after 12, 18, and 24 months. Most of the events happened between 12 and 18 months of follow-up.Conclusions:Conservative management in women younger than 30 years was safe: spontaneous regression was observed in 72% of all women younger than 30 with HSIL managed conservatively. No clinical variable was relevant, influencing regression. In 2 years the regression probability was 78%.

Prevalence of High-grade Cervical Lesion (CIN 2+) in Thai Women with High Grade Squamous Intraepithelial Lesion Cytology

Background: The prevalence of high-grade cervical intraepithelial neoplasia (CIN2+), especially invasive cancer, among Thai women with high-grade squamous intraepithelial lesion (HSIL) cytology was reported higher than in Western populations. The aim of this study was to evaluate the prevalence of underlying significant cervical lesions (CIN2+) in women with HSIL cytology. Materials and Methods: A total of 4,487 women from the Woman Health Centre of Chulabhorn Hospital, Bangkok and 1,523 women from Bangkhayaeng District of Pathumthani province, Thailand, who participated in a cervical cancer screening program between July 2011 and August 2013, were recruited into the study. A total of 22 women (14 from Chulabhorn Hospital and 8 from Bangkhayaeng District) with HSIL cytology were recruited for colposcopic evaluations. Results: Of the 22 women with HSIL cytology, the median age was 42 years (22 to 67 years). The majority of patients were multiparous (90.9%) and premenopausal (72.7%). Final pathological results were as follows: 20 (91.0%) with CIN 2, CIN3 or adenocarcinoma in situ; 0 (0%) with CIN 1; 1 (4.5%) with no epithelial lesion; and 1 (4.5%) with cervical cancer. No clinical factors were associated with CIN2+. Conclusion: Rates of CIN 2+ at initial colposcopy following HSIL cytology in our population were very high (95.5%) and support the &ldquo;see-and-treat&rdquo; strategy for HSIL cytology management. Keywords: Prevalence, Cervical intraepithelial neoplasia (CIN), High-grade squamous intraepithelial lesion (HSIL), See and treat, Thailand

Diagnostic Three Slides Pap Test Compared to Punch Biopsy and Endocervical Curettage in Confirmed HSIL+ Diagnosis.

Objective: The aim of the study was to evaluate the accuracy of the diagnostic Pap test (DPT) on three slides and punch biopsy and endocervical curettage (PB/ECC) compared with the final biopsy material in the detection of high-grade squamous intraepithelial lesion (HSIL). Materials and methods: Patients treated with conization after previous DPT and PB/ECC were analyzed. The findings of the DPT and PB/ECC as well as of the endocervical brush cytology and ECC were compared with the final conus histology. Results: 150 patients were analyzed, and final histology verified 145 cases of HSIL and 3 cancers. The percentage of confirmed HSIL cytology was 97%, while for PB/ECC it was 79% with 30/145 false negative results. The correlation between Pap test and PB/ECC showed that the diagnostic accuracy of DPT is significantly higher (p < 0.0001). Endocervical brush cytology confirmed HSIL+ in the endocervical canal in 83% and ECC in 35% of cases (p < 0.0001). Conclusion: The DPT on three slides enables better detection of HSIL compared to PB/ECC, particularly for lesions localized in the endocervical canal sampled with a cytobrush. A high quality DPT could represent a surrogate for PB/ECC and open the possibility of direct access to therapeutic procedure.

Aptima HPV messenger RNA testing and histopathologic follow‐up in women with HSIL cytology: A study emphasizing additional review of HPV‐negative cases

High-risk human papillomavirus (hrHPV) messenger RNA (mRNA) testing, the Food and Drug Administration-approved testing platform since 2013, has been increasing as a cervical screening alternative to hrHPV DNA testing methods. This study reports the largest routine clinical follow-up study reported to date of hrHPV mRNA cotesting and histopathologic follow-up results for women with high-grade squamous intraepithelial lesion (HSIL) cytology results. HSIL Papanicolaou test results for women cotested with Aptima hrHPV mRNA testing between June 2015 and November 2020 were analyzed along with recorded histopathologic follow-up results within 6 months of screening. Aptima hrHPV mRNA-positive results were reported for 95.2% of the cotested HSIL cytology cases (905 of 951). Histopathologic cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed on follow-up in 538 of 701 hrHPV mRNA-positive cases (76.8%) and in 15 of 36 hrHPV mRNA-negative cases (41.7%). Additional reviews of the hrHPV mRNA-negative HSIL cases showed variable interpretations, and confirmatory blinded-review interpretations of HSIL or atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion were more likely in cases with histopathologic CIN2+ (77.5% [93 of 120]) than those with cervical intraepithelial neoplasia grade 1 or negative findings (63.1% [101 of 160]; P < .01). This large routine-clinical-practice study confirms the previously reported high sensitivity of hrHPV mRNA testing for the detection of high-grade cervical dysplasia and cervical cancers. The blinded-review findings indicate that additional cytology review may be helpful for confirming an interpretation of HSIL in daily practice, especially for hrHPV-negative HSIL cases.

The interpretation of high-grade squamous intraepithelial lesion on anal cytology: a comparative analysis with the cervical Papanicolaou test

Prior studies have shown that high-grade squamous intraepithelial lesion (HSIL) tends to be underdiagnosed on anal cytology. Our study aims to decipher the interpretative challenges of HSIL that are more specific to anal cytology specimens by comparing them to cervical Papanicolaou tests. One hundred cases each of anal and cervical cytology specimens with HSIL interpretation and concordant histologic follow-up were retrieved and diagnostically confirmed. Patient demographic data were obtained from the electronic medical record. The cytologic specimens were reviewed and statistically compared in terms of proportion of HSIL cells, HSIL patterns and types, and cytoplasmic area of HSIL cells (with digital image analysis). A P value of <0.05 was considered statistically significant. Of the patients with anal HSIL, 97% were human immunodeficiency virus-positive and 60% were men who have sex with men. The anal cytology specimens significantly differed from the cervical ones in several respects: proportion of HSIL cells, cytoplasmic area of HSIL cells, cases with HSIL cells in syncytial groups (10 versus 57) and cases with keratinizing HSIL (45 versus 10). The P value was <0.0001 for all comparisons except for the proportion of HSIL cells (P = 0.001). Anal cytologic HSIL, in contrast to its cervical counterpart, exhibits fewer abnormal cells and smaller size of the diagnostic cells with a higher percentage of keratinizing lesions. A careful scrutiny of the sample with an enhanced understanding of the morphology and better sampling may help improve the detection of anal HSIL on cytology.

Accuracy and Efficiency of Deep-Learning-Based Automation of Dual Stain Cytology in Cervical Cancer Screening.

BackgroundWith the advent of primary human papillomavirus testing followed by cytology for cervical cancer screening, visual interpretation of cytology slides remains the last subjective analysis step and suffers from low sensitivity and reproducibility.MethodsWe developed a cloud-based whole-slide imaging platform with a deep-learning classifier for p16/Ki-67 dual-stained (DS) slides trained on biopsy-based gold standards. We compared it with conventional Pap and manual DS in 3 epidemiological studies of cervical and anal precancers from Kaiser Permanente Northern California and the University of Oklahoma comprising 4253 patients. All statistical tests were 2-sided.ResultsIn independent validation at Kaiser Permanente Northern California, artificial intelligence (AI)-based DS had lower positivity than cytology (P < .001) and manual DS (P < .001) with equal sensitivity and substantially higher specificity compared with both Pap (P < .001) and manual DS (P < .001), respectively. Compared with Pap, AI-based DS reduced referral to colposcopy by one-third (41.9% vs 60.1%, P < .001). At a higher cutoff, AI-based DS had similar performance to high-grade squamous intraepithelial lesions cytology, indicating a risk high enough to allow for immediate treatment. The classifier was robust, showing comparable performance in 2 cytology systems and in anal cytology.ConclusionsAutomated DS evaluation removes the remaining subjective component from cervical cancer screening and delivers consistent quality for providers and patients. Moving from Pap to automated DS substantially reduces the number of colposcopies and also achieves excellent performance in a simulated fully vaccinated population. Through cloud-based implementation, this approach is globally accessible. Our results demonstrate that AI not only provides automation and objectivity but also delivers a substantial benefit for women by reduction of unnecessary colposcopies.

HPV detection rates and histopathologic follow-up of patients with HSIL cytology in a large academic women’s hospital laboratory

High risk (hr) human papillomavirus (HPV) testing has been proposed as a possible replacement for Papanicolaou (Pap) cytology for cervical screening. The aim of the present study was to assess the hrHPV detection rates using 3 available Food and Drug Administration-approved HPV assays in patients with high-grade squamous intraepithelial lesion (HSIL) cytology results and to correlate the cervical screening test results with the immediate histopathologic findings. Cases with positive HSIL ThinPrep cytology findings, concurrent hrHPV testing results, and histopathologic follow-up results obtained within 6 months of the Pap/HPV co-testing were identified from July 2010 to April2018. A total of 943 HSIL Pap tests were identified with adjunctive hrHPV co-testing, and hrHPV was detected in 883 (93.6%) of these 943 cases. Cervical intraepithelial neoplasia ≥2 (CIN2+) lesions were diagnosed in 71.5% of patients, including 3.2% with invasive squamous cell carcinoma (SCC). In all hrHPV testing platforms, the detection rate for CIN2+ was significantly greater for the patients with positive HPV testing (72.7%) than for those with negative HPV testing (53.4%). However, CIN2+ lesions, including 3 cases of SCC, were found in 24 of 45 women (53.4%) with HSIL Pap and negative HPV testing results. The risk of CIN2+ histopathologic findings was significantly greater for patients with hrHPV-positive HSIL results. However, a subset of patients with HPV-negative HSIL results were found to have CIN2+ lesions, including SCC. The long-term effects of primary HPV screening on cervical cancer incidence, stage, and prognosis remain uncertain.

The Natural History of Anal High-grade Squamous Intraepithelial Lesions in Gay and Bisexual Men.

Gay and bisexual men (GBM) are disproportionately affected by anal cancer. Prevention is hindered by incomplete understanding of the natural history of its precursor, anal high-grade squamous intraepithelial lesions (HSIL). The Study of the Prevention of Anal Cancer, conducted between 2010 and 2018, enrolled human immunodeficiency virus (HIV)-positive and HIV-negative GBM aged ≥35 years. Anal cytology and high-resolution anoscopy (HRA) were performed at baseline and 3 annual visits. A composite HSIL diagnosis (cytology ± histology) was used. Cytological high-grade squamous intraepithelial lesions (cHSIL) incidence and clearance rates were calculated with 95% confidence intervals (CIs). Predictors were calculated using Cox regression with hazard ratios (HRs) and 95% CIs. Among 617 men, 220 (35.7%) were HIV-positive, median age 49 years. And 124 incident cHSIL cases occurred over 1097.3 person-years (PY) follow-up (11.3, 95% CI 9.5-13.5 per 100 PY). Significant bivariate predictors of higher incidence included age <45 years (HR 1.64, 95% CI 1.11-2.41), HIV positivity (HR 1.43, 95% CI .99-2.06), prior SIL diagnosis (P-trend < .001) and human papillomavirus (HPV)16 (HR 3.39, 2.38-4.84). Over 695.3 PY follow-up, 153 HSIL cleared (clearance 22.0, 95% CI 18.8-25.8 per 100 PY). Predictors were age < 45 years (HR 1.52, 1.08-2.16), anal intraepithelial neoplasia (AIN)2 rather than AIN3 (HR 1.79, 1.29-2.49), smaller lesions (HR 1.62, 1.11-2.36) and no persistent HPV16 (HR 1.72, 1.23-2.41). There was 1 progression to cancer (incidence 0.224, 95% CI .006-1.25 per 100 PY). These data strongly suggest that not all anal HSIL detected in screening requires treatment. Men with persistent HPV16 were less likely to clear HSIL and are more likely to benefit from effective HSIL treatments. Australia New Zealand Clinical Trials Registry (ANZCTR365383).

2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors.

2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors.

A Study of Partial Human Papillomavirus Genotyping in Support of the 2019 ASCCP Risk-Based Management Consensus Guidelines.

The 2019 ASCCP Risk-Based Management Consensus Guidelines include recommendations for partial human papillomavirus (HPV) genotyping in management of abnormal cervical cancer screening results. The guidelines are based on matching estimates of cervical intraepithelial neoplasia (CIN) 3+ risk to consensus clinical action thresholds. In support of the guidelines, this analysis addresses the risks predicted by individual identification of HPV 16 and HPV 18. Risk estimates were drawn from a subset of women in the Kaiser Permanente Northern California screening program, whose residual cervical specimens were HPV typed as part of the HPV Persistence and Progression study. We calculated risk of CIN 3+ to assess how identification of HPV 16, HPV 18, or 12 other "high-risk" HPV types would influence recommended clinical management of new abnormal screening results, taking into account current cytologic results and recent screening history. Immediate and/or 5-year risks of CIN 3+ were matched to clinical actions identified in the guidelines. Identification of HPV 16 at the first visit including HPV testing elevated immediate risk of diagnosing CIN 3+ sufficiently to mandate colposcopic referral even when cytology was Negative for Intraepithelial Lesions or Malignancy and to support a preference for treatment of cytologic high-grade squamous intraepithelial lesion. HPV 18 less clearly elevated CIN 3+ risk. Identification of HPV 16 clearly mandated consideration in clinical management of new abnormal screening results. HPV 18 positivity must be considered as a special situation because of established disproportionate risk of invasive cancer. More detailed genotyping and use beyond initial management will be considered in guideline updates.

Value of multi-quadrants biopsy: Pooled analysis of 11 population-based cervical cancer screening studies.

ObjectiveThe accuracy of colposcopy-guided biopsy is key to the success of colposcopic triage in cervical cancer screening programs. However, there is no widely adopted biopsy guideline up to date. Our study aimed to determine whether multi-quadrants biopsy improves the yield of cervical lesions.MethodsEleven population-based cervical cancer screening studies were conducted in China. Cytology, high-risk human papillomavirus (hrHPV) testing and visual inspection were performed for primary screening. Females positive on one or more tests were referred for colposcopy and biopsy. The proportion of detected cervical intraepithelial neoplasia (CIN)2+ and yields by quadrant lesion-targeted biopsy or 4-quadrant random biopsy were compared.ResultsAmong 4,923 females included, 1,606 had quadrant lesion-targeted biopsy, and 3,317 had 4-quadrant random biopsy. The cumulative CIN2+ yield increased from 0.10 for only one quadrant-targeted biopsy to 0.21, 0.34, and 0.58 for at most two, three and four quadrants targeted biopsies. Among hrHPV positive females with high-grade squamous intraepithelial lesion (HSIL)+ cytology, the cumulative CIN2+ yield of a second targeted biopsy in another quadrant was significantly increased (P<0.05). Among hrHPV-negative females, the yield of 4-quadrant random biopsies was 0.005, and the yield by lesion-targeted biopsies was 0.017. For hrHPV positive females who had 4-quadrant random biopsy, the additional CIN2+ yield for HSIL+, low-grade squamous intraepithelial lesion (LSIL) cytology, or abnormal visual inspection via acetic acid and Lugol’s iodine (VIA/VILI) were 0.46, 0.11, 0.14.ConclusionsA 4-quadrant random biopsy is recommended only for hrHPV positive females with HSIL cytology, and is acceptable if hrHPV positive with LSIL cytology or with abnormal VIA/VILI. Our findings add evidences for an objective and practical biopsy standard to guide colposcopy in cervical cancer screening programs in low- and middle-income countries.

Role of Chlamydia trachomatis serology in conservative management of cervical intraepithelial neoplasia grade 2.

To evaluate the spontaneous progression of cervical intraepithelial neoplasia grade 2 (CIN2) in accordance with Chlamydia trachomatis (chlamydia) serology. A prospective observational study included women diagnosed with CIN2 by cervical biopsy and managed conservatively for 24months at Hospital del Mar, Barcelona, between December 2011 and October 2013. Serum anti-chlamydia immunoglobulin G (IgG), previous cytology, and high-risk human papillomavirus (HPV) genotyping were recorded at baseline. The outcome was regression, persistence, or progression of CIN2. Overall, 93 women aged 18-56years were enrolled. Spontaneous regression was observed for 61 (66%) women, and 21 (23%) progressed to CIN3. Eight (9%) women had chlamydia seropositivity at baseline. Multivariate analysis showed that anti-chlamydia IgG seropositivity (odds ratio [OR], 19.1; 95% confidence interval [CI], 1.9-189.7), previous high-grade squamous intraepithelial lesion cytology (OR, 5.0; 95% CI, 1.7-14.6), and HPV16 (OR, 4.8; 95% CI, 1.7-13.7) increased the risk of CIN2 persistence or progression. Women with CIN2 and chlamydia IgG seropositivity had increased risk of progression to CIN2+ and immediate treatment may be recommended for these women. Larger clinical studies are needed to confirm the results, but chlamydia serology might be introduced into CIN2 management to better individualize treatment.

Evaluation of Risk-based Colposcopy for Cervical Precancers Detection in the ASCUS LSIL Triage Study [40B

INTRODUCTION: To validate previously shown improved efficiency of cervical precancers detection by risk-based colposcopy-biopsy in the Biopsy Study. METHODS: Included in the study were 2,453 women with ASCUS or LSIL referral cytology in the HPV triage and immediate colposcopy arms who underwent enrollment colposcopy. Enrollment cytology, HPV genotyping, and colposcopy impressions were used to establish 12 risk strata. Up to four lesion-directed cervical biopsies were taken during enrollment colposcopy. Primary outcomes were cervical intra-epithelial neoplasia grade 2 or worse disease detected by colposcopy-guided cervical biopsies at baseline and during the two-year follow up. RESULTS: The risk of detecting CIN2 or worse disease ranged from 1-85.5% across the 12 risk strata based on colposcopy impressions, study cytology, and HPV 16 status. As in the Biopsy Study, the lowest risk stratum (normal/acetowhite or benign abnormality, <HSIL cytology, and HPV 16 negative) falls below the clinical risk threshold to perform colposcopy by ASCCP guidelines; the same four risk strata with at least two of the high-risk categories (high-grade colposcopy impression, high-grade squamous intraepithelial lesion cytology, or HPV 16 positive) exceed the ASCCP recommended threshold for immediate treatment. Overall, 60-80% of women continued in the two-year study period. Except for the highest-risk strata, the negative predictive value of a negative enrollment colposcopy ranged 82.4-96% during follow-up. CONCLUSION: We show that data from the ASCUS-LSIL Triage Study confirm the risk-based colposcopy approach to improve detection of cervical precancers. Taking multiple biopsies reassures against missed disease and women with negative colposcopy may return to routine screening.

Cervical Screening Results Leading to Detection of Adenocarcinoma in Situ of the Uterine Cervix

Background:Adenocarcinoma in situ (AIS) of the uterine cervix is a preinvasive lesion of the invasive adenocarcinoma. We analyzed the cervical screening results leading to detecting the AIS lesions including the co-existence of AIS lesions with high-grade squamous intra-epithelial lesions (HSIL) and invasive carcinoma. Methods:Women who were diagnosed and received treatment for AIS at Chiang Mai University Hospital between January 1, 2007 and August 31, 2016 were retrospectively reviewed. The inclusion criteria were the women who had pathological diagnosis of AIS obtained from cervical punch biopsy or excisional cone biopsy with either loop electrosurgical excision procedure (LEEP) or cold-knife conization (CKC). The patient characteristics, diagnostic work-up and treatment details were reviewed, including the cervical screening results prior to the diagnosis of cervical AIS, pathologic results of excisional cone biopsy and hysterectomy specimens.Results:During the study period, 75 women with AIS pathology undergoing excisional cone biopsy with either LEEP (n=62) or CKC (n=13) were identified. The abnormal cytologic screening leading to detection of AIS was the squamous cell abnormality accounting for 57.3%. Abnormal glandular cytology accounted for 37.3%. The most common abnormal cervical screening results was HSIL cytology (n = 25) followed by AIS cytology (n = 13). Normal cytology was noted in 4 women in whom 3 were positive for HPV 18 and 1 had AIS on the endocervical polyp. AIS coexisted with HSIL and invasive carcinoma were detected in cone biopsy specimens in 21 (28%) and 29 (38.7%) patients, respectively. Conclusion:The majority of cervical screening results leading to detection of cervical AIS was the squamous cell abnormality accounting for 57.3% in which, HSIL cytology was the most common. Abnormal glandular cytology accounted for only 37.3%. Diagnostic cone excision is recommended if AIS lesion is noted in cervical biopsy specimen since nearly 40% have coexisting invasive lesions.

Potential influence of p16 immunohistochemical staining on the diagnosis of squamous cell lesions in cervical biopsy specimens: observation from cytologic-histologic correlation.

The p16 immunohistochemical (IHC) marker has been used increasingly as an adjunct to morphologic assessment of cervical biopsies in which the differential diagnoses include high-grade squamous intraepithelial lesion (HSIL) and its mimics. The objective of this study was to assess the potential influence of p16 IHC staining on the evaluation of cervical biopsy as observed through cytologic-histologic correlation (CHC). Cervical biopsy samples that had cytologic diagnoses of either low-grade squamous intraepithelial lesion (LSIL) or HSIL and also had histologic follow-up were retrieved from the department database. CHC and the use of p16 IHC from 2 periods (group 1, 2008; group 2, 2014-2016) were compared and analyzed. Histology on 452 samples from patients who had prior LSIL cytology in group 1 yielded 126 benign (27.9%), 272 LSIL (60.2%), and 54 HSIL (11.9%) diagnoses. By comparison, 491 samples from the patients in group 2 yielded 106 benign (21.6%), 277 LSIL (56.4%), and 108 HSIL (22.0%) diagnoses. The difference in CHC discrepancies between the 2 groups was significant (P = .0001), mainly because of the increased diagnosis of HSIL in group 2. Although p16 IHC was not applied to any sample from group 1, it was performed on 141 of 491 samples (28.7%) from group 2. Further follow-up of patients who had histologic HSIL revealed that residual HSIL was identified significantly more often in those who did not have p16 IHC applied in the preceding cervical biopsy than in those did (P = .0004). A similar comparison was performed between 113 patients from group 1 and 152 patients from group 2 who had a prior diagnosis of HSIL cytology, and the difference was statistically insignificant. The use of p16 IHC on cervical biopsies in patients who had a prior cytologic diagnosis of LSIL may lead to greater detection and upgrading of HSIL, thereby compounding the discrepancy in CHC.