Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer.

BACKGROUND: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking. METHODS: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer. RESULTS: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test). CONCLUSIONS: Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).

Factors associated with loss to follow up after abnormal cervical cancer screening in pregnancy.

OBJECTIVE: To assess risk factors associated with loss to follow up in patients referred for colposcopy after abnormal cervical cytology during pregnancy in a Southern safety net hospital population. METHODS: An urban colposcopy center was queried for patients referred for follow up of abnormal cervical cytology during pregnancy and the postpartum period. Patients were identified through a standardized referral code in the electronic medical record. Multivariable logistic regression was used to compare patient characteristics between those who followed up for colposcopy and those lost to follow up. Independent risk factors assessed included age, parity, race, insurance, HIV status, history of mental illness, BMI, gestational age and trimester at screening, cytology at colposcopy referral, interval days until colposcopy, and biopsy histology. RESULTS: 1063 patients were identified, with 40.8% of patients who completed referred colposcopy. Patient characteristics predictive for colposcopy follow up included: maternal age at referral cervical cytology >30 years (1.67; 1.27-2.20; < 0.003), gestational age < 18 weeks at abnormal cervical cytology (1.57; 1.23-2.01; <0.0002), maternal race non-African American (2.20; 1.32-3.65; <0.0024) and with high grade cervical cytology (2.42; 1.81-3.24; <0.0001). CONCLUSION: In this population, inadequate follow up for abnormal cervical cytology during pregnancy is prominent, especially among those with younger maternal age, African American (AA) race, cervical cytology completed at later gestational ages of pregnancy, and low-grade initial cytology. Higher no-show rate among AA patients supports well-documented health disparities and need for further investigation and protocols to identify those at risk for loss to follow up.

An Alternative to Cytology in Triaging Cisgender Men and Transgender Women With HIV for High-Resolution Anoscopy.

OBJECTIVES: To evaluate high-risk human papillomavirus testing (hrHPV) as an alternative for anal cytology in screening for high-grade anal neoplasia (AIN2-3) among males with HIV. To identify predictive risk factors for AIN2-3 and develop a clinical tool to triage males with HIV for high-resolution anoscopy (HRA) without cytology. DESIGN: Retrospective cohort study of 199 adult cisgender men and transgender women with HIV referred to an anal neoplasia clinic in the Southeastern United States between January 2018 and March 2021. METHODS: Each subject underwent cytology, hrHPV, and HRA. Clinical and sociodemographic risk factors were collected for each subject. Significant risk factors for AIN2-3 were identified using logistic regression, and a triage tool incorporating these factors was developed. Screening test characteristics were calculated for cytology with and without adjunct hrHPV, hrHPV alone, and the triage tool. RESULTS: In multivariate analysis, significant predictors of AIN2-3 were hrHPV positivity (odds ratio [OR] = 11.98, CI = 5.58-25.69) and low CD4 count (OR = 2.70, CI = 1.20-6.11). There was no significant difference in positive or negative predictive values among the tool, stand-alone hrHPV, and anal cytology with adjunct hrHPV. Sensitivity and specificity were not significantly different for stand-alone or adjunctive hrHPV testing. Compared with cytology, stand-alone hrHPV and the novel triage tool reduced unnecessary HRA referrals by 65% and 30%, respectively. CONCLUSIONS: Stand-alone hrHPV would have missed 11 of 74 AIN2-3 and generated 74 fewer unnecessary HRAs than current cytology-based screening patterns, which led to 115 unnecessary HRAs in our cohort. We propose triaging those with low CD4 count, hrHPV positivity, and/or smoking history for HRA.

Programmed Death Ligand-1 (PD-L1) Expression in Cervical Squamous Cell Carcinoma: Does it Correlate With Outcomes?

Cervical cancer is one of the most common gynecological malignancies. Upregulation of programmed death ligand-1 (PD-L1), an immunoregulatory protein, is associated with an adverse outcomes in several malignancies. Most studies evaluating PD-L1 expression in cervical squamous cell carcinoma (CSCC) lack data on outcomes. In this study, we correlate PD-L1 expression with clinicopathologic factors and clinical outcomes in invasive CSCC. Seventy-three cases of CSCC from 2010 to 2018 were immunostained for PD-L1. A combined positive score (CPS) of ≥1 and ≥10 was correlated with age, stage, and survival outcomes. Kaplan-Meier curves for progression-free survival and overall survival were plotted and compared using the log-rank test. Cox regression analysis was performed to identify significant prognostic factors (2-tailed P <0.05 was considered statistically significant). With CPS ≥1 or ≥10 as the cut-off, PD-L1 was positive in 52/73 (71.2%) and 23/73 (31.5%) of cases, respectively. PD-L1 positive patients present at a higher stage of disease, especially those with CPS ≥10. With CPS of ≥10 as the cut-off, the 5-yr progression-free survival and 5-yr overall survival were significantly lower ( P = 0.034 and 0.012, respectively). Only stage was statistically significant for worse overall survival on multivariate analysis. PD-L1 positive patients present at a higher stage of disease, and stage is an independent prognostic indicator for adverse outcomes in CSCC. This study highlights the potential of PD-L1 targeted therapy in patients with CSCC.

Truth or DARE (Digital Anal Rectal Examination): Gynecologist Viewpoints on Anal Cancer Screening.

METHODS: The authors conducted a survey for practicing gynecologists recruited through academic institutions, professional societies, and professional groups on social media resulting in 196 respondents. The survey, fielded between January and June 2022, included questions on knowledge, attitudes, training, and practices regarding anal cancer prevention (ACP). Descriptive statistics and χ 2 analysis were completed. RESULTS: In terms of knowledge regarding ACP, over 80% of respondents identified certain clinical indications for anal cancer screening. However, only 36% respondents selected the 3 correct ACP screening tools. Twenty-seven (13.9%) respondents reported receiving training on ACP in medical school, whereas 50 (25.9%) reported receiving training during residency. Only 21% of respondents reported that they perform anal cytology, and 32% reported that they perform digital anal rectal examinations. One hundred thirty-six respondents (75.56%) affirmed that they needed additional training on ACP to be able to provide this service to their patients, and 95 (53.1%) stated they were extremely likely to participate in ACP training if given the opportunity. CONCLUSION: Although a limited proportion of practicing gynecologists are trained in ACP, there is willingness to participate in training if it were made available and to incorporate ACP into their practices.

ASCCP Committee Opinion: Adjuvant Human Papillomavirus Vaccine for Patients Undergoing Treatment for Cervical Intraepithelial Neoplasia.

OBJECTIVES: Individuals treated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) are at long-term risk of persistent or recurrent disease despite treatment. This committee opinion aims to summarize and provide evidence-based recommendations for adjuvant human papillomavirus (HPV) vaccination based on available, published literature. METHODS: A task force from the ASCCP Practice Committee reviewed current Centers for Disease Control and Prevention (CDC) guidelines and previously published literature about the role of adjuvant HPV vaccination in previously unvaccinated individuals undergoing treatment for CIN2+ and other HPV-related diseases. RESULTS: Current CDC guidelines recommend routine or catch-up HPV vaccination for individuals aged 9 to 26 years, and shared decision making regarding vaccination for individuals aged 27 to 45 years. Multiple published studies suggest a possible benefit for adjuvant HPV vaccination in previously unvaccinated individuals undergoing treatment for CIN2+. CONCLUSIONS: The American Society for Colposcopy and Cervical Pathology recommends adherence to current CDC recommendations for vaccination of individuals aged 9 to 26 years and consideration of the possible benefit of adjuvant HPV vaccination during shared decision making for previously unvaccinated individuals aged 27 to 45 years who are undergoing treatment for CIN2+.

Factors Associated With Anal High-Grade Intraepithelial Lesions and Carcinoma Among Young Men Who Have Sex With Men and Transgender Women With HIV in Atlanta.

OBJECTIVE: This study aimed to evaluate factors associated with anal high-grade intraepithelial lesions (HSIL) and anal carcinoma among young men who have sex with men (MSM) and transgender women (TW) with HIV in Atlanta, GA, to better inform screening guidelines and preventative measures. MATERIALS AND METHODS: Cross-sectional retrospective chart review was completed for cisgender MSM and TW with HIV aged 13-25 years at the Grady Ponce and Family Youth Clinic in Atlanta, GA, from 2009 to 2020. High-grade anal disease was defined as anal intraepithelial neoplasia (AIN) 2, 3, or anal carcinoma (AIN 2+). Associations between clinical and demographic factors with AIN 2+ were estimated using logistic regression. Adjusted odds ratios (aORs) and associated 90% CIs are reported. RESULTS: One hundred nine MSM and TW with HIV who underwent anoscopy were included. One hundred three participants received anal biopsies, and 62% had AIN 2+. Being incompletely or unvaccinated against human papillomavirus (HPV, 0-2 doses) relative to being fully vaccinated (3 doses; aOR = 5.85; 90% CI = 1.28-26.83; p = .06) and having ever received surgical treatment for anogenital HPV (aOR = 2.89; 90% CI = 1.10-7.65; p = .07) were associated with AIN 2+, controlling for age and CD4 T-cell count at time of biopsy. CONCLUSIONS: Our study found a high prevalence of anal HSIL among young MSM and TW with HIV. Those who had ever received surgical treatment for anogenital HPV and those who were incompletely or unvaccinated against HPV were more likely to have HSIL. Our data emphasize the urgent need to improve HPV vaccination efforts and to pursue larger surveillance studies of anal HSIL and carcinoma among young MSM and TW with HIV.

Understanding Sexual and Gender Minority Populations and Organ-Based Screening Recommendations for Human Papillomavirus-Related Cancers.

OBJECTIVES: Sexual gender minority (SGM) populations are at risk for human papillomavirus (HPV)-related cancers of the anogenital tract and oropharynx and often face barriers to health care. The goals of this document are to clarify language to provide inclusive care for SGM populations and to provide recommendations for screening and prevention of HPV-related cancers in SGM populations. MATERIALS AND METHODS: An expert committee convened by the American Society for Colposcopy and Cervical Pathology performed a narrative review of the literature through February 2023. A comprehensive MEDLINE database search was performed for relevant studies. The literature review was divided into categories by organ/topic and by SGM population. Given the variability in available data for several of the categories, recommendations were made based on national guidelines where appropriate or expert opinion where there were less data to support risk-based guidelines. RESULTS: Definitions and terminology relevant to SGM populations are presented. The authors advocate the adoption of sexual orientation gender identity data collection and an organ-based screening approach, which is possible with knowledge of patient anatomy, sexual behaviors, and clinical history. This includes screening for cervical cancer per national recommendations, as well as screening for anal, vulvar, vaginal, penile, and oral cancers based on risk factors and shared clinical decision making. The authors recommend consideration of HPV vaccination in all SGM individuals up to age 45 years old who are at risk. CONCLUSIONS: An organ-based screening approach is part of a global strategy to create an inclusive care environment and mitigate barriers to screening and prevention of HPV-mediated cancers in SGM populations.

Promoting COVID-19 vaccine acceptance: recommendations from the Lancet Commission on Vaccine Refusal, Acceptance, and Demand in the USA.

Since the first case of COVID-19 was identified in the USA in January, 2020, over 46 million people in the country have tested positive for SARS-CoV-2 infection. Several COVID-19 vaccines have received emergency use authorisations from the US Food and Drug Administration, with the Pfizer-BioNTech vaccine receiving full approval on Aug 23, 2021. When paired with masking, physical distancing, and ventilation, COVID-19 vaccines are the best intervention to sustainably control the pandemic. However, surveys have consistently found that a sizeable minority of US residents do not plan to get a COVID-19 vaccine. The most severe consequence of an inadequate uptake of COVID-19 vaccines has been sustained community transmission (including of the delta [B.1.617.2] variant, a surge of which began in July, 2021). Exacerbating the direct impact of the virus, a low uptake of COVID-19 vaccines will prolong the social and economic repercussions of the pandemic on families and communities, especially low-income and minority ethnic groups, into 2022, or even longer. The scale and challenges of the COVID-19 vaccination campaign are unprecedented. Therefore, through a series of recommendations, we present a coordinated, evidence-based education, communication, and behavioural intervention strategy that is likely to improve the success of COVID-19 vaccine programmes across the USA.

Thirty-day Postoperative Adverse Events in Minimally Invasive versus Open Abdominal Radical Hysterectomy for Early-stage Cervical Cancer.

STUDY OBJECTIVE: To identify the incidence, type, and grade of postoperative adverse events in minimally invasive radical hysterectomy vs abdominal radical hysterectomy (ARH) for patients with early-stage cervical cancer and determine risk factors associated with these adverse events. DESIGN: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) was queried to identify patients with early-stage cervical cancer undergoing radical hysterectomy. Multivariable logistic regression was used to assess risk factors associated with adverse postoperative outcomes among patients undergoing radical hysterectomy. SETTING: ACS NSQIP participating institutions within the United States. PATIENTS: Patients were collected from the ACS NSQIP databases (2014-2017) undergoing radical hysterectomy for early-stage cervical cancer. INTERVENTIONS: N/A MEASUREMENTS AND MAIN RESULTS: ARH had a significantly increased incidence of any 30-day postoperative adverse event compared with minimally invasive radical hysterectomy (31.2% vs 19.9%, p <.001). There was a higher incidence of surgical site infection, both deep and superficial, and blood transfusions in ARH. On multivariable logistic regression, the abdominal surgical approach was the only risk factor significantly associated with any postoperative adverse event (odds ratio, 1.4; confidence interval, 1.1-1.9; p = .018; 95% CIs). CONCLUSIONS: In this study, the abdominal surgical approach for radical hysterectomy in early-stage cervical cancer was associated with a higher incidence of postoperative adverse events than the minimally invasive approach.

Perceptions of Anal Cancer Risk Among HIV-Positive and High-Risk HIV-Negative Women.

OBJECTIVES: Women living with HIV (WLWH) have a greater risk of anal cancer than women without HIV; however, there are limited studies that examine awareness of anal cancer risk among WLWH and "high-risk" HIV-negative women. This study examines risk factors for anal cancer, perceptions of risk for anal cancer, and perceptions of anal cancer screening among a cohort of WLWH and high-risk HIV-negative women. MATERIALS AND METHODS: From the Atlanta, GA, and Bronx, NY, sites of the Women's Interagency HIV Study, 155 WLWH and HIV-negative women were enrolled and the Champion Health Belief Model Scale questionnaire measuring risk perceptions to anal cancer was administered to each participant. RESULTS: The WLWH perceived anal cancer to be less serious and perceived facing fewer barriers to anal cancer screening than HIV-negative women (both p = .01). Older women (≥50 years) felt that they had less barriers to anal cancer screening (p = .047). Moreover, women who had less than a high school education felt more susceptible to anal cancer (p = .001), as did women who reported a history of anal intercourse (p = .017). CONCLUSIONS: Despite being at an increased risk for anal cancer, perceptions of susceptibility to anal cancer and seriousness of anal cancer were low among WLWH. These findings highlight opportunities for provider and patient educational interventions to improve awareness of anal cancer risk among WLWH.

Primary HPV and Molecular Cervical Cancer Screening in US Women Living With Human Immunodeficiency Virus.

BACKGROUND: Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomavirus (oncHPV) testing as the initial cervical cancer screening method and typically, if positive, additional reflex-triage (eg, HPV16/18-genotyping, Pap testing). While US guidelines support PHS usage in the general population, PHS has been little studied in women living with HIV (WLWH). METHODS: We enrolled n = 865 WLWH (323 from the Women's Interagency HIV Study [WIHS] and 542 from WIHS-affiliated colposcopy clinics). All participants underwent Pap and oncHPV testing, including HPV16/18-genotyping. WIHS WLWH who tested oncHPV[+] or had cytologic atypical squamous cells of undetermined significance or worse (ASC-US+) underwent colposcopy, as did a random 21% of WLWH who were oncHPV[-]/Pap[-] (controls). Most participants additionally underwent p16/Ki-67 immunocytochemistry. RESULTS: Mean age was 46 years, median CD4 was 592 cells/µL, 95% used antiretroviral therapy. Seventy WLWH had histologically-determined cervical intraepithelial neoplasia grade 2 or greater (CIN-2+), of which 33 were defined as precancer (ie, [i] CIN-3+ or [ii] CIN-2 if concurrent with cytologic high grade squamous intraepithelial lesions [HSILs]). PHS had 87% sensitivity (Se) for precancer, 9% positive predictive value (PPV), and a 35% colposcopy referral rate (Colpo). "PHS with reflex HPV16/18-genotyping and Pap testing" had 84% Se, 16% PPV, 30% Colpo. PHS with only HPV16/18-genotyping had 24% Colpo. "Concurrent oncHPV and Pap Testing" (Co-Testing) had 91% Se, 12% PPV, 40% Colpo. p16/Ki-67 immunochemistry had the highest PPV, 20%, but 13% specimen inadequacy. CONCLUSIONS: PHS with reflex HPV16/18-genotyping had fewer unnecessary colposcopies and (if confirmed) could be a potential alternative to Co-Testing in WLWH.

The ASCCP Cervical Cancer Screening Task Force Endorsement and Opinion on the American Cancer Society Updated Cervical Cancer Screening Guidelines.

ABSTRACT: The American Cancer Society (ACS) released updated cervical cancer screening guidelines in 2020 that endorse a shift in practice to primary human papillomavirus (HPV) screening in people with a cervix, beginning at ages of 25-65 years. When access to US Food and Drug Administration-approved primary HPV testing is not available, the ACS offers cotesting or cytology as acceptable alternative strategies but suggests that these testing modalities may be excluded from future iterations of the guidelines. The ASCCP recognizes the benefits and risks of primary HPV cervical cancer screening while acknowledging the barriers to widespread adoption, including implementation issues, the impact of limited HPV vaccination in the United States, and inclusion of populations who may not be well represented on primary HPV screening trials, such as underrepresented minorities. The ASCCP endorses the 2018 US Preventive Services Task Force Recommendation Statement and supports the ACS cervical cancer screening guidelines. Most importantly, the ASCCP endorses any cervical cancer screening for secondary prevention of cervical cancer and recommends interventions that improve screening for those who are underscreened or unscreened.

Criminal Justice Involvement and Abnormal Cervical Cancer Screening Results Among Women in an Urban Safety Net Hospital.

OBJECTIVE: The aim of the study was to elucidate the risk factors underlying abnormal cytology-based cervical cancer screening (Pap testing) in justice-involved women (JIW) compared with non-JIW in an urban safety net hospital. METHODS: Retrospective chart review of women with a history of correctional involvement who received care at Grady Health System between 2010 and 2018 and had a Pap test was performed (n = 191). An age-matched cohort of women with no correctional involvement and had a Pap test at Grady served as the control (n = 394). Variables of interest were age, HIV, smoking, race, mental health history, and history of incarceration. Outcomes of interests were rate of abnormal Pap tests and follow-up. χ2 and logistic regression models evaluated associations between the variables of interest and outcomes. RESULTS: Rates of abnormal Pap tests were significantly higher in JIW (35.6%) than controls (18.5%, p < .0001). Compared with controls, JIW were significantly more likely to have high-grade cervical cytology (odds ratio [OR] = 3.89, p < .0005) and be lost to gynecologic follow-up (OR = 8.75, p < .0001) and a history of severe mental illness (29.5% vs 4.3%, p < .0001). Those with abnormal Pap tests were likely to be HIV-positive (OR = 20.7, p < .001) and have a history of incarceration (OR = 2.33, p < .001). Predictors of high-grade Pap test were smoking history (OR = 0.16, p = .014), HIV-positive (OR = 3.66, p = .025), and history of incarceration (OR = 3.96, p < .0005). CONCLUSIONS: Justice-involved women represent a high-risk subpopulation with significantly increased rates of high-grade cytology and lost to follow-up. This underscores the need for attention to screening programs and follow-up interventions for JIW.

Pilot Study of Markers for High-grade Anal Dysplasia in a Southern Cohort From the Women's Interagency Human Immunodeficiency Virus Study.

BACKGROUND: Anal cancer rates have increased, particularly in human immunodeficiency virus (HIV)-infected (HIV+) women. We assessed factors associated with anal precancer in HIV+ and at-risk HIV-negative women from the Atlanta Women's Interagency HIV Study cohort. METHODS: All participants underwent high-resolution anoscopy and anal cytology and had anal and cervical samples collected. Specimens were tested for 37 human papillomavirus (HPV) types and for FAM19A4 and microRNA124-2 promoter methylation. Binary logistic regression and multivariate analysis were conducted with histologic anal high-grade squamous intraepithelial lesion (A-HSIL) as the dependent variable. RESULTS: Seventy-five women were enrolled: 52 (69%) were HIV+ with three-fourths having undetectable viral load; 64 (86%) were black; mean age was 49 ± 8 years. Forty-nine (65%) anal cytology samples were abnormal, and 38 (51%) of anal samples were positive for at least 1 of 13 high-risk HPV (hrHPV) types. Thirteen (18%) anal biopsies identified A-HSIL. Hypermethylation of FAM19A4 and/or microRNA124-2 was found in 69 (95%) anal samples and 19 (26%) cervical samples. In multivariate analyses, the odds of having A-HSIL were >6 times higher in women with anal hrHPV (adjusted odds ratio [aOR], 6.08 [95% confidence interval {CI}, 1.27-29.18], P = .02) and with positive cervical methylation (aOR, 6.49 [95% CI, 1.66-25.35], P = .007), but not significantly higher in women with positive anal methylation. CONCLUSIONS: Anal hrHPV and promoter hypermethylation in the cervix show promise as biomarkers for anal cancer screening in HIV+ and at-risk HIV-negative women. Greater understanding of gene silencing by promoter hypermethylation in anal carcinogenesis is needed.

Epidemiological evidence that common HPV types may be common because of their ability to evade immune surveillance: Results from the Women's Interagency HIV study.

Infection by human papillomavirus (HPV) type 16, the most oncogenic HPV type, was found to be the least affected by HIV-status and CD4 count of any of the approximately 13 oncogenic HPV types. This relative independence from host immune status has been interpreted as evidence that HPV16 may have an innate ability to avoid the effects of immunosurveillance. However, the impact of immune status on other individual HPV types has not been carefully assessed. We studied type-specific HPV infection in a cohort of 2,470 HIV-positive (HIV[+]) and 895 HIV-negative (HIV[-]) women. Semi-annually collected cervicovaginal lavages were tested for >40 HPV types. HPV type-specific prevalence ratios (PRs), incidence and clearance hazard ratios (HRs), were calculated by contrasting HPV types detected in HIV[+] women with CD4 < 200 to HIV[-] women. HPV71 and HPV16 prevalence had the weakest associations with HIV-status/CD4 count of any HPV, according to PRs. No correlations between PRs and HPV phylogeny or oncogenicity were observed. Instead, higher HPV type-specific prevalence in HIV[-] women correlated with lower PRs (ρ = -0.59; p = 0.0001). An alternative (quadratic model) statistical approach (PHIV+ = a*PHIV- + b*PHIV- 2 ; R2 = 0.894) found similar associations (p = 0.0005). In summary, the most prevalent HPV types in HIV[-] women were the types most independent from host immune status. These results suggest that common HPV types in HIV[-] women may have a greater ability to avoid immune surveillance than other types, which may help explain why they are common.

Diagnosing Anal Squamous Intraepithelial Lesions With and Without p16: An Interobserver Variability Study.

OBJECTIVE: Morphologic diagnosis and grading of anal squamous intraepithelial lesions (ASILs) are challenging. In this study, we investigated interobserver variability and p16 utility in accurately grading anal SIL. MATERIALS AND METHODS: Six pathologists evaluated the degree of SIL on hematoxylin and eosin slides from 146 anal biopsies, followed by the review of both p16 and hematoxylin and eosin slides in cases where p16 was previously performed. κ was calculated in the following 4 ways: (A) 4-tiered diagnosis (negative for SIL [NSIL], anal intraepithelial neoplasia [AIN 1, AIN 2, AIN 3]); (B) 3-tiered diagnosis (NSIL and AIN 1 [pooled], AIN 2, AIN 3); (A) 3-tiered diagnosis (NSIL, low-grade SIL, high-grade SIL [HSIL]); and (D) 2-tiered diagnosis (no HSIL, HSIL). RESULTS: There is only moderate agreement with a 4-tiered diagnosis with or without p16 (κ = 0.48-0.57). There is substantial agreement when AIN 2 and AIN 3 are pooled as HSIL in cases with or without p16 review (κ = 0.71-0.78). There is almost perfect agreement with a 2-tiered diagnosis of negative for HSIL and HSIL both in cases where p16 was used and where p16 was not required, with the best agreement for a 2-tiered diagnosis with concurrent p16 review. CONCLUSIONS: This study highlights the importance of a judicious use of p16 for diagnosis. When there is no need for p16 by the Lower Anogenital Squamous Terminology guidelines, interobserver agreement was substantial to almost perfect with a 2-tiered diagnosis. However, when its use is indicated but it is not performed or reviewed, the agreement is much lower even with a 2-tiered diagnosis. Rational use of p16 will ensure diagnostic accuracy and the best possible patient care.

Do High Rates of Atypical Glandular Cells Correlate With Higher Incidence of Disease in a Large Safety Net Hospital.

OBJECTIVE: The aim of the study was to describe the incidence and correlates of atypical glandular cell (AGC) Pap tests in a low socioeconomic status, underserved population. MATERIALS AND METHODS: Medical records of patients with AGC Pap tests at a single institution were reviewed from January 2013 to August 2019. Baseline characteristics were extracted including age, body mass index, birth control, abnormal uterine bleeding, and human papillomavirus (HPV). All colposcopy and endometrial biopsies were classified into negative/low-risk (polyps, tubular metaplasia, microglandular hyperplasia, cervical intraepithelial neoplasia 1) and high-risk (HR) lesions (cervical intraepithelial neoplasia 2/3, adenocarcinoma in situ, endometrial hyperplasia, cervical cancer, endometrial cancer). Logistic regression identified significant associations. Sixty-eight randomly selected AGC cytology slides from the cohort and 32 non-AGC slides outside the cohort were blindly reviewed by 6 pathologists. Fleiss κ interrater agreement was assessed. RESULTS: Seven hundred forty patients with AGC Pap tests were identified (0.8% of all Pap tests performed during this time). After excluding for incomplete data, 478 patients were included. Sixty-three patients had HR lesions (13.3%). Patients with HR lesions had increased odds of abnormal uterine bleeding (odds ratio = 4.32, p < .001) and HPV positivity (odds ratio = 10.89, p < .001) when compared with patients with low-risk lesions. The κ agreement was 0.21 for all cases and 0.18 for AGC alone. CONCLUSIONS: This population falls within the national averages for AGC Pap tests. There was an increased risk of HR lesions in patients with abnormal uterine bleeding and HPV positivity. The rate of HR lesions among AGC Pap tests was at the lower end of values in the literature. After blinded pathologist review, interobserver κ agreement was low for AGC Pap tests.

Knowledge of Anal Cancer, Anal Cancer Screening, and HPV in HIV-Positive and High-Risk HIV-Negative Women.

The incidence of anal cancer in HIV-positive women is a growing public health concern where they have a 7.8-fold increased risk for anal cancer than women in the general population. We examined knowledge of anal cancer, anal cancer screening, and HPV in HIV-positive women and high-risk HIV-negative women. Women were recruited from the Women's Interagency HIV Study and completed an adapted Knowledge of Anal Cancer and HPV Scale. Correlations among anal cancer knowledge and sociodemographic and risk factors were assessed using Pearson's or Spearman's rho r test. Student's t test or chi-square tests identified significant differences between groups by HIV status or risk factors. Among 155 women, 72% (n = 113) correctly identified the purpose of an anal Pap test. However, only 42% (n = 65) identified HIV as a risk factor for anal cancer. HIV-positive women were more knowledgeable about anal cancer than high risk HIV-negative women (t = 2.104, p = .037). Women with a history of an abnormal cervical Pap test (t = 2.137, p = .034), younger age (t = 3.716, p = .000), reported history of anal sex (t = 3.284, p = .001), some college education or higher (t = -2.005, p = .047), and non-smokers (t = 2.425, p = .016) were significantly more knowledgeable about HPV. Although most women were knowledgeable about anal cancer, many women could not identify important risk factors for anal cancer, such as HIV infection. Patient educational interventions tailored to HIV-positive women are warranted to improve knowledge and awareness of risk for anal cancer.