Detection Of High-grade Squamous Intraepithelial Lesions Research Articles

Methylation markers for anal cancer screening: A repeated cross-sectional analysis of people living with HIV, 2015-2016.

People living with HIV (PLWH) are at highest risk of anal cancer and will benefit from optimized screening for early disease detection. We compared host DNA methylation markers in high-grade squamous intraepithelial lesions (HSIL) versus samples negative for intraepithelial lesions (NILM) or low-grade intraepithelial lesions (LSIL) in PLWH. We recruited PLWH identifying as male aged ≥18 years undergoing high-resolution anoscopy (HRA) in Seattle, Washington, 2015-2016. Anal brush samples were collected for HPV detection, genotyping, and pyrosequencing methylation (host genes ASCL1, PAX1, FMN2, and ATP10A); clinical data were abstracted from medical records. We assessed associations between methylation and presence and extent of HSIL using generalized estimating equation logistic regression, adjusting for age, CD4 count and HIV viral load. Marker panels using HPV DNA and methylation were also evaluated to predict prevalent HSIL. We analyzed 125 samples from 85 participants (mean age 50.1; standard deviation 11.0 years). ASCL1 (adjusted odds ratio [aOR] per 1 unit increase mean percent methylation: 1.07, 95% CI: 1.01-1.13) and FMN2 (aOR per 1 unit increase mean percent methylation: 1.14, 95% CI: 1.08-1.20) methylation were significantly associated with HSIL versus NILM/LSIL. ASCL1 (aOR: 1.06, 95% CI: 1.01-1.11) and FMN2 (aOR: 1.13, 95% CI: 1.08-1.17) methylation were positively associated with increasing HSIL extent. A panel combining methylation (ASCL1 and FMN2) and HPV DNA (HPV16, HPV18, and HPV31) demonstrated best balance of sensitivity (78.2%) and specificity (73.9%) for HSIL detection compared with methylation or HPV alone. Increasing levels of DNA methylation of ASCL1 and FMN2 were positively associated with HSIL detection in PLWH. Host gene methylation testing shows promise for HSIL screening and triage.

Cumulative detection of anal high-grade squamous intraepithelial lesions over two-year follow-up in men who have sex with men living with HIV in France.

We assessed cumulative detection and determinants of anal high-grade squamous intraepithelial lesions (HSIL) in men who have sex with men living with HIV who underwent three visits over two years, with cytology and high-resolution anoscopy (HRA), within the ANRS-EP57-APACHES study. Cumulative HSIL detection was 33% (134/410), of which 48% were detected at baseline. HSIL detection varied considerably by center (13-51%). Strongest HSIL determinants were baseline HPV16 (adjusted odds ratio [aOR] 8.2; 95% confidence interval [95%CI] 3.6-18.9), and p16/Ki67 (aOR 4.6; 95%CI 2.3-9.1). Repeat annual cytology and HRA improved HSIL detection but did not fully compensate between-center heterogeneity.

Microbiome-derived cobalamin and succinyl-CoA as biomarkers for improved screening of anal cancer.

Human papillomavirus can cause preinvasive, high-grade squamous intraepithelial lesions (HSILs) as precursors to cancer in the anogenital area, and the microbiome is suggested to be a contributing factor. Men who have sex with men (MSM) living with human immunodeficiency virus (HIV) have a high risk of anal cancer, but current screening strategies for HSIL detection lack specificity. Here, we investigated the anal microbiome to improve HSIL screening. We enrolled participants living with HIV, divided into a discovery (n = 167) and validation cohort (n = 46), and who were predominantly (93.9%) cisgender MSM undergoing HSIL screening with high-resolution anoscopy and anal biopsies. We identified no microbiome composition signatures associated with HSILs, but elevated levels of microbiome-encoded proteins producing succinyl coenzyme A and cobalamin were significantly associated with HSILs in both cohorts. Measurement of these candidate biomarkers alone in anal cytobrushes outperformed anal cytology as a diagnostic indicator for HSILs, increasing the sensitivity from 91.2% to 96.6%, the specificity from 34.1% to 81.8%, and reclassifying 82% of false-positive results as true negatives. We propose that these two microbiome-derived biomarkers may improve the current strategy of anal cancer screening.

Evaluating the performance of anal cytology and high-risk HPV genotyping for detecting anal HSIL in a clinic-based sample of people living with and without HIV in Puerto Rico.

Given the disproportionately elevated anal cancer risk in high-risk populations, it is important to assess the performance of commonly used anal cancer screening tools to improve the effectiveness of detection and treatment methods. This study evaluates 1) the concordance between anal cytology and histology results and 2) the performance of cytology and high-risk human papillomavirus (HR-HPV) genotyping as screening tools for detecting histologically confirmed anal high-grade squamous intraepithelial lesions (HSIL). Data from the Anal Neoplasia Clinic in Puerto Rico (2014-2021; n = 466) was used. The clinical performance of anal cytology and HR-HPV genotyping to detect HSIL was compared to the gold standard: high-resolution anoscopy-guided biopsy. Sensitivity, specificity, positive predictive value, negative predictive value, and κ coefficients were calculated. A total of 66.95% of the patients were men, 74.0% were people living with HIV, 76.2% had anal HR-HPV infection, and 40.34% had histologically confirmed anal HSIL. The weighted κ statistic between the tests (cytology and histology) was 0.25 (p < .001). The sensitivity and specificity of cytology alone to detect anal HSIL were 84.3% (95% confidence interval [CI], 78.3%-89.1%) and 36.0% (95% CI, 30.3%-42.0%), respectively. Anal HR-HPV genotyping had higher sensitivity (92.2%; 95% CI, 87.4%-95.6%) and similar specificity (34.8%; 95% CI, 29.2%-40.7%) compared to cytology. The two tests combined (positive results following cytology or HR-HPV test) improved sensitivity to detect anal HSIL (97.9%; 95% CI, 94.8%-99.4%), but specificity was compromised (19.2%; 95% CI, 14.7%-24.4%). Although HR-HPV genotyping improved the detection of anal HSIL, HR-HPV testing had lower specificity than anal cytology alone.

Immediate histopathologic correlation in Turkish population with negative cytology and high-risk human papillomavirus positivity: A retrospective analysis of high-risk human papillomavirus genotype and stratified by age.

According to the American Society of Colposcopy and Cervical Pathology (ASCCP) recommendations, regardless of age, women with high-risk infections other than human papillomavirus 16/18 positivity (other hrHPV) and negative cytology should not be referred directly to colposcopy. Several studies compared detection rates of ≥high-grade squamous intraepithelial lesion (HSIL) between HPV 16/18 ± 45, and other hrHPV types on colposcopic biopsy. We designed a retrospective study to determine the presence of ≥HSIL in colposcopic biopsy in women with negative cytology and hrHPV positivity during the years 2016-2022. HPV 16/18/45 had a PPV of 43.8%, while other hrHPV types had a PPV of 29.1% for a tissue diagnosis of ≥HSIL. For a tissue diagnosis of ≥HSIL detection, there was no statistically significant difference between the PPV of other hrHPV and HPV 16/18/45 in patients ≥30. There were only two cases with a tissue diagnosis of ≥HSIL in the other hrHPV group of women under 30 years of age. We suggested that the follow-up recommendations of ASCCP for patients above the age of 30 with negative cytology and other hrHPV positivity may not be fully applicable to countries like Turkey with a different healthcare environment. Referring to patients ≥30 who had other hrHPV positivity and negative cytology to direct colposcopy may be clinically beneficial, particularly in populations where a colposcopic examination is easy and inexpensive.

HPV Cotesting of Unsatisfactory Papanicolaou Tests: Implications for Follow-up Intervals.

The 2019 American Society of Colposcopy and Cervical Pathology management guidelines recommend that patients with an unsatisfactory Papanicolaou (Pap) test (UPT) and negative human papillomavirus (HPV) cotest undergo repeat age-based screening in 2 to 4 months. The rationale is that a negative HPV test in the setting of an UPT may reflect an inadequate sample and therefore should not be interpreted as truly "negative." For patients 25 years and older who are cotested, if HPV is positive for the 16 or 18 genotypes, direct referral for colposcopy is recommended. Our study aimed to determine if a negative HPV cotest result is predictive of the absence of a high-grade squamous intraepithelial lesion (HSIL) and whether these patients may be called back for repeat testing at an interval longer than 2 to 4 months. Follow-up cervical cytology and biopsy results in women with UPT and HPV cotests from January 2017 to December 2021 were collected. Original UPT and HPV cotest results were correlated with the follow-up Pap and biopsy results. There were 1,496 (2.28%) UPT cases out of 65,641 total Pap tests. Among the 1,496 UPT cases, 1,010 (67.5%) had HPV cotesting; 676 (45.1%) were followed by repeat Pap or biopsy within 4 months and 850 (56.8%) within 12 months. The total follow-up rate was 81%, with a range of 3 days to 36 months. The HSIL rate in HPV-positive cases was 5.7% (3/53) vs 0.4% (2/539) (P = .006) in HPV-negative cases. In UPT, HPV cotesting showed negative predictive values for low-grade and high-grade squamous intraepithelial lesion detection of 98.5% and 99.6%, respectively, while positive predictive values were 19% and 5.7%. A negative HPV cotest in individuals with UPT predicted the lack of HSIL in our study. Compliance with the recommended follow-up time of 2 to 4 months for women with UPT was low (45.1%). Our study suggests that women with UPT and negative HPV cotest may be safely called back at an interval longer than 4 months.

Value of p16 Expression in the Detection of High-Grade Squamous Intraepithelial Lesion of Cervix

Background: Cervical intraepithelial neoplasia (CIN) is usually a precancerous condition but, if left untreated, can develop into invasive cervical cancer. CIN2 and CIN3 are combinedly termed high-grade squamous intraepithelial lesions (HSIL). There are few screening tests based on cytology in detecting HSIL, but they are mostly less accurate. There is over-expression of p16 in pre-cancer and cancer of the cervix. The purpose of this study was to determine the value of p16 expression in the detection of HSIL. Methods: It was a cross-sectional study conducted in the colposcopy clinic of the Department of Obstetrics and Gynecology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from October 2021 to March 2022. The study included 72 HSIL patients detected by colposcopy and had subsequent cervical biopsy and p16 immunohistochemistry. Results: Majority (45.8%) of the patients were found within the 30-39 years age group, 44.4% of the participants were illiterate, and 76.4% came from the middle-income group. Colposcopy-directed cervical Punch or Loop electrosurgical excision procedure (LEEP) biopsy revealed that 70.5% of patients had HSIL, and the rest (64.3%) suffered from LSIL. Positive p16 results were significantly higher among the HSIL group (84.1%) compared to those other than the HSIL group (3.6%) (p&lt;0.001). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the p16 in the detection of HSIL were 84.1%, 96.4%, 79.4%, and 88.9%, respectively. Conclusions: Immunohistochemistry for p16 has a high diagnostic value in detecting HSIL patients. Therefore, this could be recommended for appropriate management of patients with CIN to avoid misdiagnosis and the over or under-treatment.

Convolutional neural network-based classification of cervical intraepithelial neoplasias using colposcopic image segmentation for acetowhite epithelium

Colposcopy is a test performed to detect precancerous lesions of cervical cancer. Since cervical cancer progresses slowly, finding and treating precancerous lesions helps prevent cervical cancer. In particular, it is clinically important to detect high-grade squamous intraepithelial lesions (HSIL) that require surgical treatment among precancerous lesions of cervix. There have been several studies using convolutional neural network (CNN) for classifying colposcopic images. However, no studies have been reported on using the segmentation technique to detect HSIL. In present study, we aimed to examine whether the accuracy of a CNN model in detecting HSIL from colposcopic images can be improved when segmentation information for acetowhite epithelium is added. Without segmentation information, ResNet-18, 50, and 101 achieved classification accuracies of 70.2%, 66.2%, and 69.3%, respectively. The experts classified the same test set with accuracies of 74.6% and 73.0%. After adding segmentation information of acetowhite epithelium to the original images, the classification accuracies of ResNet-18, 50, and 101 improved to 74.8%, 76.3%, and 74.8%, respectively. We demonstrated that the HSIL detection accuracy improved by adding segmentation information to the CNN model, and the improvement in accuracy was consistent across different ResNets.

Impact of a High-Resolution Anoscopy Clinic on Management of Anal Dysplasia in Women Living With HIV.

The rate of anal squamous cell cancer (aSCC) is increasing among women living with HIV. Treatment of precursor high grade squamous intraepithelial lesions (HSIL) may reduce the risk of progression to aSCC. The objective of this study was to examine effects of a dedicated high-resolution anoscopy (HRA) clinic on management of HSIL in women with HIV. Women living with HIV who underwent anal dysplasia screening at a single institution between 2006 and 2020 were reviewed. Those who underwent screening before (Group A) and after (Group B) the implementation of an HRA program in 2017 were compared. The primary outcome of interest was the successful detection and treatment of HSIL. A total of 201 women living with HIV underwent anal dysplasia screening between 2006 and 2020. Seventy-seven patients were found to have abnormal anal cytology requiring further treatment: 43 (55.8%) in Group A and 34 (44.2%) patients in Group B. Of the patients with abnormal anal cytology, 76.7% of patients in Group A received further biopsy and treatment, whereas 79.4% of Group B patients underwent subsequent biopsy and treatment. In propensity score weighting logistic regression analysis, the Group B was 4.6 times as likely to diagnosis HSIL on biopsy compared to Group A (OR = 4.60, 95% CI: 1.15 to 18.38, P = .03). Anal dysplasia is common among women living with HIV. The establishment of a HRA program was associated with increased identification and treatment of HSIL among women living with HIV, which may prevent the progression to aSCC.

Abstract 2241: Evaluating anal cancer screening approaches in high-risk populations in Puerto Rico

Abstract Introduction: Anal cancer incidence has been rising rapidly in Puerto Rico. The ANCHOR study showed that treating high-grade squamous intraepithelial lesions (HSILs) significantly reduces anal cancer incidence. Limited research has been done to understand the validity and associated costs of screening tools used to detect anal lesions in Hispanic populations. We aimed to evaluate the clinical performance (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) and screening test costs in the clinic-based sample. Understanding the accuracy and costs of screening tools can guide interventions in resource-limited settings to broaden the availability of effective, low-cost screening options and promote anal cancer prevention. Methods: The cross-sectionally analyzed data was collected (May 2015 - June 2021) by the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Cancer Center. The clinic predominantly serves referred adults (≥18 years old). Patients were included in the analyses if they had complete results for anal cytology, high-resolution anoscopy (HRA) with biopsy, and anal high-risk HPV (HR-HPV) typing (n=436). Sensitivity, specificity, PPV, and NPV were estimated to evaluate the clinical performance of anal cytology alone and in combination with HR-HPV typing in the detection of histologically confirmed anal HSIL (Gold standard). Analyses were stratified by risk group (women, MSM, and heterosexual men) and HIV status. Evaluation of cost-effective alternative screening strategies is currently ongoing. Results: The mean age of our sample was 44 ± 13 years; more than half (67%) were male. HIV-infected MSM, HIV-infected women, and HIV-negative MSM comprised 45.4%, 22.2%, 13.3% of our sample, respectively. 40% of the sample had HSIL and 69% tested positive for HR-HPV. Measured against the gold standard, we found that co-testing (anal cytology and HR-HPV typing) increased the sensitivity in the groups evaluated and decreased specificity in some. Among HIV-infected MSM, the sensitivity of anal cytology alone to detect HSIL was 84.7%, whereas specificity was 30.0%. Although the sensitivity of the 2 tests combined (anal cytology and HR-HPV typing) to detect histologically confirmed HSIL increased (91.8%), the specificity decreased (22.0%). Overall, the sensitivity of cytology alone was higher in women compared to men and among PLWH compared to HIV-negative individuals. Conclusion: While higher sensitivity for HSIL detection was seen for cytology alone for women and HIV-infected populations, co-testing increased the sensitivity for HSILs detection. Understanding the accuracy and cost of screening tools can guide interventions to broaden the availability of effective, low-cost screening options and promote anal cancer prevention. Access and availability of these tools in a wide context of communities must be considered. Citation Format: Kandyce G. Keller, Celeste Leigh Pearce, Karen J. Ortiz-Ortiz, Jeslie M. Ramos-Cartagena, Humberto Guiot, Vivian Colón-López, Ashish A. Deshmukh, Maribel Tirado-Gómez, Ana Patricia Ortiz. Evaluating anal cancer screening approaches in high-risk populations in Puerto Rico [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2241.

Role of ProEx C immunocytochemistry in cervical high-grade squamous intraepithelial lesions detection.

Background: Screening programs using Papanicolaou smear along with human papillomavirus (HPV) testing led to a significantly decrease of cervical cancer rates. Nevertheless, both assessments have limited specificity for revealing cervical high-grade lesions. The main problem is how to identify the real precursor of cervical squamous cell carcinomas (SCC), namely high-grade squamous intraepithelial lesions (HSIL). Aim: The aim of our study was to conclude if ProEx C might be used as a marker for high-grade cervical intraepithelial neoplasia (CIN). Materials and Methods: In this study, we detected the immunochemical expression of anti-ProEx C antibody in liquid-based cytology (LBC) samples. We analyzed a total number of 125 cervical cytology specimens. Results: In 48% of all cases, ProEx C was found to be positive. The percentage increased from 0% in negative for intraepithelial lesion or malignancy (NILM) cases to 100% in SCC cases. Conclusions: ProEx C may be utilized to improve the accuracy of cytological diagnosis on cervical smears, according to the findings of this study. This marker is also useful in detecting unrevealed high-grade lesions on atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesions (LSIL) smears, being very useful in establishing the conduct of these cases.

Liquid-Based Cytology in the Detection of Premalignant Lesions in Patients with "Atypia in Squamous Cells" in Conventional Cytology.

The management of patients with "Atypical Squamous Cells" (ASC) in conventional papanicolaou smears (CPS) is based on the risk of high-grade squamous intraepithelial lesion (HSIL). The efficacy of liquid-based cytology (LBC) to detect this premalignant lesion is variable, with little evidence of its performance in Colombian patients. The aim of this study is to determine the performance of LBC in the detection of premalignant lesions, in patients with ASC in CPS. Were obtained patients who attended colposcopy clinic due the result of ASC in CPS. An LBC was taken, which was interpreted by two pathologists without access to other results. The performance of LBC to detect HSIL, was determined, considering as a gold standard: histopathological study/negative-satisfactory colposcopy. Were included 114 patients, with a mean age of 38.4 years (SD ± 13.3). LBC had abnormal results in 40.36% (n = 46), with a slightly higher proportion of low-grade squamous intraepithelial lesion (LSIL) than HSIL. The total of abnormal diagnoses by colposcopy and/or biopsy was 51.75% (n = 59), with a predominance of LSIL (36.84%). The sensitivity of the liquid-based cytology to detect premalignant lesions was 76.5%, specificity: 66.0%, positive predictive value: 28.3% and negative predictive value: 94.1%; The Cohen's kappa index of LBC for detecting HSIL was 0.2492 for the total population and 0.2907 for ≥30 years. Although LBC decreases abnormal cytology and increases the detection of HSIL, which improves diagnostic accuracy; sensitivity and predictive values for detecting HSIL are not significantly different between CPS and LBC.

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.

High Prevalence of Anal High-Grade Squamous Intraepithelial Lesions, and Prevention Through Human Papillomavirus Vaccination, in Young Men Who Have Sex With Men Living With Human Immunodeficiency Virus

BackgroundMen who have sex with men (MSM) are at high risk for human papillomavirus (HPV)–related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied.MethodsTwo hundred and sixty MSMLWH aged 18–26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24.ResultsAmong 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type–associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18–associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events.Conclusions18–26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type–associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.

The reporting rates of high-grade squamous intraepithelial lesions and their human papillomavirus testing and histologic follow-up results: A comparison between ThinPrep and SurePath preparations.

Liquid-based cytology (LBC) tests SurePath (SP) and ThinPrep (TP) have largely replaced conventional Papanicolaou (Pap) tests for cervical cytology screening due to higher sensitivity. However, comparison between SP and TP test sensitivity and efficacy in detecting squamous abnormalities is lacking. Our study aims to compare high-grade squamous intraepithelial lesion (HSIL) reporting rates, human papillomavirus (HPV) positivity rates, and histologic outcome between these two LBC methods. We performed a retrospective search of the period between January 2014 and June 2017, when both TP and SP were utilized at our institution, to identify HSIL cases and collect the HPV testing and histologic follow-up results for those cases. One hundred twenty-five HSILs were identified from the 15 382 TP specimens (0.81%) and 93 HSILs were identified from the 25 105 SP specimens (0.37%), a statistically significant difference (P < .0001). The corresponding HPV positivity rates were 95.6% and 89.7% in TP-HSILs and SP-HSILs, respectively, a statistically non-significant difference. Histologic follow-up showed HSILs or carcinomas were identified in 78% (49/63) of TP-HSILs and 79% (45/57) of SP-HSILs, with no statistically significant difference. TP demonstrated a higher HSIL detection rate than SP with no significant difference in follow-up HPV or histologic results.

Human Papillomavirus Vaccination Prior to Loop Electroexcision Procedure Does Not Prevent Recurrent Cervical High-grade Squamous Intraepithelial Lesions in Women Living With Human Immunodeficiency Virus: A Randomized, Double-blind, Placebo-controlled Trial.

Women living with human immunodeficiency virus (HIV), especially in sub-Saharan Africa, are at high risk for cervical high-grade squamous intraepithelial lesions (HSIL) and cervical cancer. These women have high HSIL recurrence rates after loop electroexcision procedure (LEEP). Retrospective studies suggest that human papillomavirus (HPV) vaccination improves response to treatment of cervical HSIL. We performed a double-blind, randomized clinical trial enrolling 180 women living with HIV in Johannesburg, South Africa, diagnosed with cervical HSIL by colposcopic biopsy. Women received quadrivalent HPV vaccine or placebo (1:1) at entry, week 4, and week 26. LEEP was performed at week 4. Colposcopic-directed biopsies and cervical cytology were performed at weeks 26 and 52. The primary endpoint, cervical HSIL by histology or cytology at either week 26 or 52, was compared between arms using χ 2 analysis. Participant characteristics included median age of 39 years and median CD4 count 489 cells/μL, and 94% had HIV suppression. One hundred seventy-four women completed the vaccine/placebo series and had evaluable results at week 26 or 52. The proportion experiencing the primary endpoint was similar in the vaccine and placebo groups (53% vs 45%; relative risk, 1.18 [95% confidence interval, .87-1.6]; P = .29). HSIL recurrence was associated with a LEEP biopsy result of HSIL and detection of HSIL at the margins of the LEEP sample. This study did not support HPV vaccination to prevent recurrent HSIL after LEEP in women living with HIV. Recurrent HSIL was high despite virologic suppression. Improved treatments are needed for HSIL to reduce the burden of cervical cancer among women living with HIV. NCT01928225.

High-Resolution Anoscopy Surveillance After Anal Squamous Cell Carcinoma: High-Grade Squamous Intraepithelial Lesion Detection and Treatment May Influence Local Recurrence.

BACKGROUND:Local recurrence is a significant risk after anal squamous cell carcinoma.OBJECTIVES:This study aimed to examine the occurrence of high-grade squamous intraepithelial lesions and local recurrence after anal cancer at surveillance with high-resolution anoscopy.DESIGN:This is a retrospective observational study.SETTING:This study was conducted at an anogenital neoplasia referral center.PATIENTS:There were 76 anal/perianal cancers from 1998 to 2018. Sixty-three patients were eligible and 3 were excluded, for a total of 60 patients; 35 of 60 (58%) patients were male.INTERVENTION:High-resolution anoscopy after chemoradiation or excision only for anal squamous cell carcinoma was performed.MAIN OUTCOME MEASURES:The primary outcomes measured were local recurrence and high-grade squamous intraepithelial lesion detection rates.RESULTS:Sixty patients, 27% HIV positive, underwent surveillance over a median 42 (range 7–240) months of follow-up. Seven had had a prior local recurrence at study entry so were analyzed separately. Thirty of 53 underwent chemoradiation (57%) and 23 of 53 underwent excision alone (43%); 33 had perianal cancer and 20 had anal cancer. Ten of 30 of the chemoradiation group had had stage 1 (33%) disease in comparison with 22 of 23 of the excision only group (96%, p < 0.001).OUTCOMES:High-grade squamous intraepithelial lesions were detected in 4 of 30 (13%) patients after chemoradiation and in 17 of 23 (74%) patients after excision only (p < 0.001). Twenty of 21 (95%) high-grade lesions were treated with ablation. Six of 7 (86%) patients with prior local recurrence had high-grade squamous intraepithelial lesions over a median of 21 months follow-up. One local recurrence (T1N0M0) occurred during surveillance after primary chemoradiation (0.56/1000 person-months), none occurred after excision only, and 2 of 7 with prior local recurrence developed further local recurrence (6.86/1000 person-months). All 3 local recurrences occurred after treatment of high-grade squamous intraepithelial lesions. There were no metastases, abdominoperineal excisions, or deaths from anal squamous cell carcinoma.LIMITATIONS:Retrospective data were used for this study.CONCLUSIONS:High-grade squamous intraepithelial lesions after anal squamous cell carcinoma are more common after excision only than after chemoradiation. Local recurrence is low in this high-resolution anoscopy surveillance group in which high-grade squamous intraepithelial disease was ablated. Excision of small perianal cancers appears safe; however, a subset of patients is at excess risk. See Video at http://links.lww.com/DCR/B285.VIGILANCIA POR ANOSCOPÍA DE ALTA RESOLUCIÓN EN CASOS DE CARCINOMA ANAL A CÉLULAS ESCAMOSAS: LA DETECCIÓN Y TRATAMIENTO DE UNA LESIÓN INTRAEPITELIAL ESCAMOSA DE ALTO GRADO (HSIL) PUEDE INFLUIR EN LA RECURRENCIA LOCALANTECEDENTES:La recurrencia local tiene un riesgo significativo después del carcinoma anal a células escamosas.OBJETIVO:Evaluar la aparición de lesiones intraepiteliales escamosas de alto grado (HSIL) y su recurrencia local durante la vigilancia con anoscopía de alta resolución en casos de cancer anal.DISEÑO:Estudio observacional retrospectivo.AJUSTE:Centro de referencia de neoplasia anogenital.PACIENTES:Se diagnosticaron 76 cánceres anales / perianales entre 1998 y 2018. Un total de 63 pacientes fueron elegidos, 3 excluidos (n = 60), 35/60 (58%) fueron varones.INTERVENCIÓN:Anoscopía de alta resolución después de la quimio-radioterapia, o solo excisión en casos de carcinoma anal a células escamosas.PRINCIPALES MEDIDAS DE RESULTADO:Recurrencia local primaria y tasas de detección de lesión intraepitelial escamosa de alto grado.RESULTADOS:Sesenta pacientes, 27% VIH positivos, fueron sometidos a vigilancia durante una mediana de 42 (rango 7–240) meses de seguimiento. Siete habían tenido una recurrencia local antes de ser incluidos en el estudio, por lo que se analizaron por separado. Treinta de 53 se sometieron a quimio-radioterapia (57%) y 23/53 solo a excisión (43%). 33 eran lesiones perianales, 20 de canal anal. 10/30 del grupo de quimio-radioterpia se encontraban en Fase 1 (33%) comparados con 22/23 del grupo de excisión (96%, p <0.001).RESULTADOS:Se detectaron lesiones intraepiteliales escamosas de alto grado en 4/30 (13%) después de la quimio-radioterapia, y en 17/23 (74%) solo después de la excisión (p < 0.001). 20/21 (95%) lesiones de alto grado fueron tratadas con ablación. Seis de siete (86%) con recurrencia local previa tenían lesiones intraepiteliales escamosas de alto grado durante una mediana de seguimiento de 21 meses. Se produjo una recurrencia local (T1N0M0) durante la vigilancia después de la quimio-radioterapia primaria (0.56/1000 persona-meses), ninguna después de la excisión sola y 2/7 con recurrencia local previa desarrollaron una recurrencia local adicional (6.86/1000 persona-meses). Las 3 recidivas locales ocurrieron después del tratamiento de las lesiones intraepiteliales escamosas de alto grado. No hubieron metástasis, excisiones abdominoperineales o muertes por carcinoma anal a células escamosas.LIMITACIONES:Datos retrospectivos.CONCLUSIONES:Las lesiones intraepiteliales escamosas de alto grado en casos de carcinoma escamocelular anal son más comunes después de la excisión sola que después de la quimio-radioterapia. La recurrencia local es baja en este grupo de vigilancia de anoscopía de alta resolución en el que se retiró la enfermedad intraepitelial escamosa de alto grado. La excisión de pequeños cánceres perianales parece segura; sin embargo, un subconjunto de pacientes tiene un riesgo excesivo. Consulte Video Resumen en http://links.lww.com/DCR/B285. (Traducción—Dr. Xavier Delgadillo)

Abstract 5771: Performance of uterine cervix liquid based cytology, in patients with ASCUS by conventional pap smear

Abstract Background: The diagnosis of uterine cervix premalignant lesions is ​​the goal of cervical cancer prevention programs; Conventional Pap smear (CPS) with its limitations remains the screening method used in these programs in many Latin-American countries. In Colombia, after the implementation of CPS as a primary screening test, a less than expected decrease in mortality from cervical cancer has been observed. Actions aimed to improving cytological diagnosis could reduce the number of patients followed and treated unnecessarily. The demonstration of high specificity for liquid-based cytology (LBC) to adequately categorize cases with ASCUS in CPS, will serve as support for public health authorities, in their decisions about the best method to the screening programs. Design: Were included all patients with ASCUS results in CPS, referred to a Cervical Pathology Unit in Cartagena, Colombia. Material for LBC was obtained and LBCs were interpreted by two pathologists, blind to previous CPS or colposcopy diagnosis. Colposcopy were classified as negative/normal and positive/abnormal, colposcopic abnormalities were biopsied. Histological analyzes were performed by two pathologists blind to CBL outcome. Pathology diagnosis used were: CIN1/HPV infection: low-grade squamous intraepithelial lesion (LSIL), CIN2/CIN3: high-grade squamous intraepithelial lesion (HSIL). Diagnostic gold standards used to calculate LBC performance were: normal/negative for SIL: if colposcopy did not reveal lesion or colposcopy was abnormal but biopsy revealed no lesion; abnormal/positive: biopsy diagnosis ≥CIN2. Sensitivity, specificity, positive (PPV), negative predictive values (NPV), ​​ and Kappa concordance and correlation test were performed. Results: A total of 114 cases taken from patients with ASCUS in CPS were included, 77 of them corresponded to patients ≥30 years old. LBC sensitivity and specificity to detect HSIL/≥CIN2 were 76.5% and 66.0% respectively; PPV and NPV were 28.3% and 94.1%, when the cut-off point was a cytological result of HSIL. The concordance with the histological study was k = 0.2492 (p= 0.01). LBC is possible to reduce doubtful results and colposcopy remissions. Using LBC there were fewer results of ASCUS which is the most common cytological abnormality in screening populations that imposes heavy burden for follow-up. Concordance in HSIL cases with histological study was 100%, but in general the accuracy measured by the kappa statistic is low. Conclusions: These results support the evidence that LBC is no more sensitive than CPS for detection of HSIL/≥CIN2. The sensitivity and predictive values for HSIL/≥CIN2 were not significantly different between CPS and LBC, but, taking into account the benefits of unsatisfactory minors, and material availability for molecular biomarkers and HPV detection in the same sample, it could be used in cervical cancer program management guidelines. Citation Format: Ines Benedetti, Yoled Vizcaino, Lia Barrios. Performance of uterine cervix liquid based cytology, in patients with ASCUS by conventional pap smear [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5771.

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.

Risk of cervical lesions in high-risk HPV positive women with normal cytology: a retrospective single-center study in China

BackgroundTo investigate high-risk HPV (hr-HPV) genotype distributions and the association between hr-HPV infection with severity of the cervical lesions in women with normal cytology.MethodsIn this cross-sectional study, the result of the hr-HPV test and biopsy of colposcopy of women with normal cytology from January 2012 to January 2019 were analyzed. The detection rate of high-grade squamous intraepithelial lesion (HSIL) and cervical cancer were calculated among different hr-HPV genotypes, viral load group, and age groups.ResultsFive thousand eight hundred eighty women were enrolled in this study. Overall, 59.97% had normal histological results, 19.32% had HSIL, and 1.07% had cervical cancer. The detection rate of HSIL or worse (HSIL+) in women with single HPV16(34.00%), HPV31(27.50%), HPV33(25.58%), and HPV52(20.88%) infection were higher significantly than single HPV18 (15.59%) infection, respectively. The HSIL+ detection rate between HPV16 single infection and multiple infections (excluding HPV18) was no significant difference (34% vs 35.47%, P = 0.638), contrary to HPV18(12.59% vs 21.67%, P = 0.022). In women without HPV16/18 infections, HSIL+ detection rates for single, double, and triple or more hr-HPV infections were 12.28, 20.31, and 37.50%, the risk of detection of HSIL+ significantly increasing. With the hr-HPV DNA load increases, the risk of detection of HSIL+ (χ2 = 91.01, P < 0.0001) and invasive cervical cancer (χ2 = 5.757, P = 0.016) increase. In age < 30, 31–40, 41–50, 51–60, > 60 group, HSIL+ detection rate were 24.80%、22.10%、19.59%、14.29, and 12.61%, respectively.ConclusionWomen who have normal cytology with HPV 16/18/31/33/52/58 infections, multiple HPV infections and high viral load, have a higher detection rate of HSIL+.