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Objective: To describe the findings of high-resolution anoscopy (HRA) in human immunodeficiency virus (HIV)-infected women with a history of lower genital tract dysplasia.Materials and Methods: A retrospective chart review of all HIV-infected women undergoing HRA from 2002 to 2003 was conducted. Demographic and clinical information, including the most recent cervical and vaginal cytologic results and colposcopic evaluations, were collected from medical records. These data were compared with anal cytologic and histologic findings from HRA.Results: Eight patients were identified, with a mean age of 42 years. The mean duration of known HIV infection was 12 years. All eight patients had a previous history of treatment for cervical dysplasia or carcinoma. Five patients also had a history of high-grade vulvar dysplasia. The most recent cervical and vaginal cytologic results for all patients were abnormal. Seven patients underwent HRA because of suspected anal intraepithelial neoplasia (AIN); of these, four patients had perianal warts and three had diffuse high-grade vulvar dysplasia. One patient was referred for HRA because of high-grade dysplasia on vaginal cytologic analysis with a negative colposcopic and urologic evaluation. All eight patients (100%) had abnormal anal cytologic results with histologically proven AIN. Five patients had AIN 2,3, and three patients had AIN 1 and anal condyloma. Two of the three patients with AIN 1 had high-grade perianal dysplasia.Conclusions: High-resolution anoscopy identified anal dysplasia in 100% of eight HIV-infected women with human papilloma virus-related dysplasia of the lower genital tract. High-resolution anoscopy should be considered as part of the evaluation for the extent of disease in HIV-infected women with cervical and vaginal dysplasia, condyloma, and dysplasia of the perineum. [ABSTRACT FROM AUTHOR]

This study aimed to describe the prevalence of high-risk human papillomavirus (HR-HPV) types in the anal canal in a cohort of people living with HIV (PLWHIV) with a history of malignancy., Setting: Referral tertiary care hospital for adult patients with cancer., Methods: We reviewed data of patients from the AIDS Cancer Clinic on antiretroviral therapy in chronic control who were consecutively referred for high-resolution anoscopy (HRA), where they underwent anal evaluation, collection of specimens for anal cytology and anal human papillomavirus (HPV) followed by HRA with directed biopsy if needed., Results: A total of 155 patients were included; 149 (96.1%) were men, all of them men who have sex with men (MSM); the median age was 39 (IQR 32-47) years; 105 (67.7%) with Kaposi sarcoma, 40 (25.8%) with non-Hodgkin lymphoma and 10 (6.4%) with other neoplasms; only 7 (4.5%) had active cancer. The prevalence of HR-HPV infection was 89% (n=138) (95% CI 83-93) with at least one HR-HPV infection, and 62% (96) had coinfection with at least two types; the median HR-HPV types of coinfection were 3 (IQR 2-4). The number of patients infected with HPV 16 was 64 (41.3%, 95% CI 33.8-49.3), HPV 18 was 74 (47.7%, 95% CI 39.9-55.7) and with both 35 (22.6%). Some 59 patients (38%) had high-grade squamous intraepithelial lesions (HSIL) and 49 (31.6%) had low-grade squamous intraepithelial lesions (LSIL). The prevalence of HR-HPV and HSIL among patients aged ≤35 and >35 years was the same., Conclusions: In this cohort of PLWHIV with a history of malignancy we found a high prevalence of HR-HPV 16 and 18 and anal HSIL, even in persons aged ≤35 years. These data highlight the importance of anal cancer screening in PLWHIV and history of malignancy., (© 2024 British HIV Association.)

The International Anal Neoplasia Society (IANS) developed consensus guidelines to inform anal cancer screening use among various high-risk groups. Anal cancer incidence estimates by age among risk groups provided the basis to identify risk thresholds to recommend screening. Guided by risk thresholds, screening initiation at age 35 years was recommended for men who have sex with men (MSM) and transgender women (TW) with HIV. For other people with HIV and MSM and TW not with HIV, screening initiation at age 45 years was recommended. For solid organ transplant recipients, screening initiation beginning from 10 years post-transplant was recommended. For persons with a history of vulvar precancer or cancer, screening initiation was recommended starting within 1 year of diagnosis of vulvar precancer or cancer. Persons aged ≥45 years with a history of cervical/vaginal HSIL or cancer, perianal warts, persistent (>1 year) cervical HPV16, or autoimmune conditions could be considered for screening with shared decision-making, provided there is adequate capacity to perform diagnostic procedures (high-resolution anoscopy [HRA]). Anal cytology, high-risk (hr) human papillomavirus (HPV) testing (including genotyping for HPV16), and hrHPV-cytology co-testing are different strategies currently used for anal cancer screening that show acceptable performance. Thresholds for referral for HRA or follow-up screening tests are delineated. These recommendations from IANS provide the basis to inform management of abnormal screening results, considering currently available screening tools. These guidelines provide a pivotal foundation to help generate consensus among providers and inform the introduction and implementation of risk-targeted screening for anal cancer prevention., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Detection and treatment of anal histologic high-grade squamous intraepithelial lesions (hHSIL) prevents anal cancer. However, anal hHSIL incidence among women with human immunodeficiency virus (HIV, WHIV) remains unknown. Performance of anal high-risk human papillomavirus ([hr]HPV), anal cytology (anal-cyt), and both for hHSIL detection longitudinally over 2 years also remains undetermined., Methods: We determined 2-year incidence and cumulative risk estimates (2-y-CR) of anal hHSIL among WHIV using prevalence and incidence (per 100 person-years [py]) observations stratified by baseline hrHPV and/or anal-cyt results., Results: In total, 229 WHIV with complete baseline data were included in the analysis; 114 women without prevalent anal hHSIL were followed with 2 annual evaluations. Median age was 51, 63% were Black, and 23% were Hispanic. Anal hrHPV or abnormal anal-cyt was associated with an increased risk of incident anal hHSIL at 2 years (18.9/100py [95% confidence interval {CI} 11.4-31.3] and 13.4/100py [95% CI 8.0-22.7], respectively) compared with no detection of anal HPV or negative cytology (2.8/100py [95% CI 1.1-7.4] and 4.2 [95% CI, 1.8-10.2]) The presence of anal hrHPV with abnormal cytology was associated with 2-y-CR of anal hHSIL of 65.6% (95% CI 55.4%-75%); negative hrHPV with negative cytology was associated with 2-y-CR of anal hHSIL of 9.2% (95% CI 7.0-16.0)., Conclusions: Detection of anal hrHPV or abnormal anal cytology are comparable predictors for 2-y-CR of anal hHSIL. The absence of anal hrHPV combined with negative cytology was predictive of a lower (but measurable) risk of developing anal hHSIL. These findings provide important data to inform anal cancer screening guidelines for WHIV., Competing Interests: Potential conflicts of interest. J. M. P. reports consulting fees from Vir Biotechnologies, Roche Diagnostics, Abbott, Antiva Biosciences, and Merck and Co.; consulting fees and stock options from Virion Therapeutics; travel support from Merck and Co.; an unpaid role with the International Papillomavirus Society; research support to University of California, San Francisco (UCSF) and gifts from Atila Biosystems. M. H. E. reports research support to institution from J&J, Pfizer, Inovio, PDS Biotechnologies, AstraZeneca, Imvax, Iovance, B-D, and Zentalis; consulting fees (paid to institution) from Papivax, Merck, B-D, PDS Biotechnologies, and World Health Organization; travel support for meetings from Merck and Zentalis; and participation on Merck's Advisory Board for HPV research. T. W. reports institutional grants or contracts from Merck; payment or honoraria for speaking engagements from ViiV Healthcare and Merck; travel support and donation of vaccine for trials from Merck. E. A. S. reports travel support from National Cancer Institute and ASCCP; and board membership with ASCCP. R. A. L. reports a role on their institutions data safety monitoring board. H. M. G. reports a contract with the University of Puerto Rico; honoraria for lectures from Salud Integral de la Montana, American College of Physicians, and Infectious Diseases Society of Puerto Rico; payment for expert testimony (21-CV-001169-FAB; CG2020CV01235 (Caguas, 101); C DP2015-0062, Arecibo); travel support from University of Puerto Rico School of Medicine; and unpaid roles as President of Infectious Diseases Society of Puerto Rico and membership on the Puerto Rico Medical Task Force for COVID-19. A. L. F. reports institutional grants from NIH. G. E. reports honoraria from Northeast/Caribbean AIDS Education and Training Center (NECA AETC) and International AIDS Society – USA (IAS-USA). A. A. D. reports consulting fees from Value Analytics Lab unrelated to the current work. LFB reports an unpaid role as President of International Anal Neoplasia Society. N. J. reports Board membership for International Anal Neoplasia Society. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Copyright © 2023, ASCCP.)

Purpose: To determine whether treatment of anal high-grade squamous intraepithelial lesions (HSIL), vs active monitoring, is effective in reducing incidence of anal cancer in persons living with HIV, the US National Cancer Institute funded the Phase III ANal Cancer/HSIL Outcomes Research (ANCHOR) clinical trial. As no established patient-reported outcomes (PRO) tool exists for persons with anal HSIL, we sought to estimate the construct validity and responsiveness of the ANCHOR Health-Related Symptom Index (A-HRSI)., Methods: The construct validity phase enrolled ANCHOR participants who were within two weeks of randomization to complete A-HRSI and legacy PRO questionnaires at a single time point. The responsiveness phase enrolled a separate cohort of ANCHOR participants who were not yet randomized to complete A-HRSI at three time points: prior to randomization (T1), 14-70 (T2), and 71-112 (T3) days following randomization., Results: Confirmatory factor analysis techniques established a three-factor model (i.e., physical symptoms, impact on physical functioning, impact on psychological functioning), with moderate evidence of convergent validity and strong evidence of discriminant validity in the construct validity phase (n = 303). We observed a significant moderate effect for changes in A-HRSI impact on physical functioning (standardized response mean = 0.52) and psychological symptoms (standardized response mean = 0.60) from T2 (n = 86) to T3 (n = 92), providing evidence of responsiveness., Conclusion: A-HRSI is a brief PRO index that captures health-related symptoms and impacts related to anal HSIL. This instrument may have broad applicability in other contexts assessing individuals with anal HSIL, which may ultimately help improve clinical care and assist providers and patients with medical decision-making., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This review presents the epidemiology, pathophysiology, prevention, and management of sexually transmitted human papillomavirus (HPV) and its associated diseases. HPV is the most common sexually transmitted infection worldwide. Prevalence varies regionally. Low-risk strains cause anogenital warts, which can be managed with patient- or provider-applied therapies. High-risk strains cause lower anogenital cancers. Primary and secondary prevention strategies include vaccination and screening for precancerous lesions, respectively. Management of abnormal screening results vary by test result, anatomic site, and individual cancer risk. Approaches include close rescreening, high-resolution visualization with biopsy, and-when biopsy-proven precancer is identified-removal or destruction of the lesion., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Given the increasing availability of radiation therapy in sub-Saharan Africa, clinical trials that include radiation therapy are likely to grow. Ensuring appropriate delivery of radiation therapy through rigorous quality assurance is an important component of clinical trial execution. We reviewed the process for credentialing radiation therapy sites and radiation therapy quality assurance through the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center for AIDS Malignancy Consortium (AMC)-081, a multicenter study of cisplatin and radiation therapy for women with locally advanced cervical cancer living with HIV, conducted by the AIDS Malignancy Consortium at 2 sites in South Africa and Zimbabwe., Methods and Materials: Women living with HIV with newly diagnosed stage IB2, IIA (>4 cm), IIB-IVA cervical carcinoma (per the 2009 International Federation of Gynecology and Obstetrics [FIGO] staging classifications) were enrolled in AMC-081. They received 3-dimensional conformal external beam radiation therapy (EBRT) to the pelvis (41.4-45 Gy) using a linear accelerator, high-dose-rate brachytherapy (6-9 Gy to point A with each fraction and up to 4 fractions), and concurrent weekly cisplatin (40 mg/m 2 ). IROC reviewed EBRT and brachytherapy quality assurance records after treatment., Results: All of the 38 women enrolled in AMC-081 received ±5% of the protocol-specified prescribed dose of EBRT. Geometry of brachytherapy applicator placement was scored as per protocol in all implants. Doses to points A and B, International Commission on Radiation Units and Measurements (ICRU) bladder, or ICRU rectum required correction by IROC in >50% of the implants. In the final evaluation, 58% of participants (n = 22) were treated per protocol, 40% (n = 15) had minor protocol deviations, and 3% (n = 1) had major protocol deviations. No records were received within 60 days of treatment completion as requested in the protocol., Conclusions: Major radiation therapy deviations were low, but timely submission of radiation therapy data did not occur. Future studies, especially those that include specialized radiation therapy techniques such as stereotactic or intensity-modulated radiation therapy, will require pathways to ensure timely and adequate quality assurance., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Squamous cell carcinoma of the anus (SCCA) incidence and mortality rates are rising in the United States. Understanding state-level incidence and mortality patterns and associations with smoking and AIDS prevalence (key risk factors) could help unravel disparities and provide etiologic clues., Methods: Using the US Cancer Statistics and the National Center for Health Statistics data sets, we estimated state-level SCCA incidence and mortality rates. Rate ratios (RRs) were calculated to compare incidence and mortality in 2014-2018 versus 2001-2005. The correlations between SCCA incidence with current smoking (from the Behavioral Risk Factor Surveillance System) and AIDS (from the HIV Surveillance system) prevalence were evaluated using Spearman's rank correlation coefficient., Results: Nationally, SCCA incidence and mortality rates (per 100,000) increased among men (incidence, 2.29-3.36, mortality, 0.46-0.74) and women (incidence, 3.88-6.30, mortality, 0.65-1.02) age ≥ 50 years, but decreased among men age < 50 years and were stable among similar-aged women. In state-level analysis, a marked increase in incidence (≥ 1.5-fold for men and ≥ two-fold for women) and mortality (≥ two-fold) for persons age ≥ 50 years was largely concentrated in the Midwestern and Southeastern states. State-level SCCA incidence rates in recent years (2014-2018) among men were correlated ( r = 0.47, P < .001) with state-level AIDS prevalence patterns. For women, a correlation was observed between state-level SCCA incidence rates and smoking prevalence ( r = 0.49, P < .001)., Conclusion: During 2001-2005 to 2014-2018, SCCA incidence and mortality nearly doubled among men and women age ≥ 50 years living in Midwest and Southeast. State variation in AIDS and smoking patterns may explain variation in SCCA incidence. Improved and targeted prevention is needed to combat the rise in SCCA incidence and mitigate magnifying geographic disparities.

Competing Interests: I declare funding from the NIH and no competing interests.

To inform optimal approaches for detecting anal precancers, we performed a systematic review and meta-analysis of the diagnostic accuracy of anal cancer screening tests in different populations with elevated risk for anal cancer. We conducted a literature search of studies evaluating tests for anal precancer and cancer (anal intraepithelial neoplasia grade 2 or worse, AIN2+) published between January 1, 1997 to September 30, 2021 in PubMed and Embase. Titles and abstracts were screened for inclusion and included articles underwent full-text review, data abstraction and quality assessment. We estimated the prevalence of AIN2+ and calculated summary estimates and 95% confidence intervals (CI) of test positivity, sensitivity and specificity and predictive values of various testing strategies, overall and among population subgroups. A total of 39 articles were included. The prevalence of AIN2+ was 20% (95% CI, 17-29%), and ranged from 22% in men who have sex with men (MSM) living with HIV to 13% in women and 12% in MSM without HIV. The sensitivity and specificity of cytology and HPV testing were 81% and 62% and 92% and 42%, respectively, and 93% and 33%, respectively for cytology and HPV co-testing. AIN2+ risks were similar among those testing positive for cytology, HPV, or co-testing. Limited data on other biomarkers (HPV E6/E7 mRNA and p16/Ki-67 dual stain), suggested higher specificity, but lower sensitivity compared with anal cytology and HPV. Our findings provide important evidence for the development of clinical guidelines using anal cytology and HPV testing for anal cancer screening., (© 2022 UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

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.)., (Copyright © 2022 Massachusetts Medical Society.)

Objective: This study explores provider preferences regarding anal cancer screening indications, initiation age, tools, and referral threshold to high resolution anoscopy (HRA)., Methods: International Anal Neoplasia Society affiliates were invited to complete an online survey. Options for initiation age and tools were delineated by sub-groups. HRA referral thresholds separately queried recommendations by patient immune status., Results: One hundred forty respondents participated. Although consensus was lacking with regard to specific screening initiation age, more respondents recommended younger initiation ages for men who have sex with men (MSM) living with HIV (LWH) compared with MSM not LWH (p < 0.01). "No age threshold" ranged 44-55% among sub-groups with lower genital tract disease. Cytology and digital anorectal exam (DARE) were the most frequently selected tools for all sub-groups (ranges 77-90% and 74-86%, respectively). HRA was recommended significantly more frequently for MSM LWH (58%) and patients with vulvar cancer (52%) compared to others (p < 0.01). "Any [test] abnormality" was more often selected as indication for HRA for immunocompromised (56%) and immunocompetent (46%) patients than a specific cytology test result (29%, 36% respectively)., Conclusion: Cytology and DARE were preferred screening tools; screening initiation age and HRA referral threshold showed less consensus. Evidence-based guidelines are needed and may lead to more consistent screening practices., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

In June 2019 the Centers for Disease Control and Prevention (CDC) convened an advisory group to assist in development of the 2021 CDC sexually transmitted infections (STI) guidelines. The advisory group on anal cancer screening and prevention met to formulate key questions in this field. The group examined published literature and abstracts to assess evidence and give recommendations for development of the CDC guidelines. This article summarizes key questions, evidence, recommendations, and areas for further research for the screening, diagnosis, and prevention of anal cancer., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

It is well established that persons living with HIV (PLWH) have highly elevated rates of anal HSIL and anal cancer compared with those who are not living with HIV. The 5-year risk of anal cancer following anal HSIL has been reported to be as high as 14.1% among PLWH compared with 3.2% among those who are not living with HIV. To address these concerns, the AIDS Malignancy Consortium completed a large-scale, randomized trial to compare strategies for the prevention of anal cancer among PLWH with anal HSIL. The objective of the study was to determine whether treating anal HSIL was effective in reducing the incidence of anal cancer in PLWH compared with active monitoring. This paper describes the design of the ANal Cancer/HSIL Outcomes Research Study (ANCHOR) with respect to estimating the anal cancer event rate in this high risk population., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Men 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., Methods: Two 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., Results: Among 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., Conclusions: 18-26-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 Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objective: Recommendations for the age of initiating screening for cervical cancer in women with HIV (WWH) in the United States have not changed since 1995 when all women (regardless of immune status) were screened for cervical cancer from the age of onset of sexual activity, which often occurs in adolescence. By 2009, recognizing the lack of benefit as well as harms in screening young women, guidelines were revised to initiate cervical cancer screening for the general population at age 21 years. By comparing cervical cancer incidence in young WWH to that of the general population, we assessed the potential for increasing the recommended age of initiating cervical cancer screening in WWH., Design: We compared age-specific invasive cervical cancer (ICC) rates among WWH to the general population in the United States HIV/AIDS Cancer Match Study., Methods: We estimated standardized incidence ratios as the observed number of cervical cancer cases among WWH divided by the expected number, standardized to the general population by age, race/ethnicity, registry, and calendar year., Results: ICC rates among WWH were elevated across all age groups between ages 25 and 54 years (SIR = 3.80; 95% CI 3.48--4.15) but there were zero cases among ages less than 25 years., Conclusion: The absence of ICC among WWH less than 25 years supports initiating cervical cancer screening at age 21 years, rather than adolescence, to prevent cancers in WWH at ages with higher risk of ICC., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This study investigated the clinical outcomes for patients with pelvic ultrasound findings suspicious for uterine arteriovenous malformations (AVMs) at a single institution. We reviewed the electronic medical record to identify women with pelvic ultrasound reports read as possible uterine AVM, and used medical records to determine clinical outcomes. Among the 39 women with ultrasounds suspicious for AVM, 14 had subsequent MRIs, 10 had additional ultrasounds, and 10 underwent pelvic angiography. Five of the 39 women were ultimately diagnosed with AVMs. Of the 34 women who did not have an AVM, 12 were diagnosed with retained products of conception. Women may be receiving overtreatment for possible uterine AVMs; careful clinical consideration is warranted as the most common clinical diagnosis for women with radiologic findings suspicious of uterine AVM is retained products of conception.Impact statement What is already known on the subject: An acquired uterine arteriovenous malformation (AVM) is an abnormal arterio-venous connection in the myometrium that may cause life-threatening haemorrhage. Over the past decade, it has been noted that the characteristic ultrasound findings of uterine AVM may represent other causes of uterine hypervascularity including retained products of conception. What the results of this study add: As there is no consensus on the management of highly vascular myometrial lesions suspicious for uterine AVMs, this study reports our institution's experience with pelvic ultrasound findings suspicious for uterine AVMs. We found that further diagnostic workup, including MRI and angiography were common, but that the most frequent final diagnosis was retained products of conception. What the implications are of these findings for future clinical practice: This study contributes to the growing body of work noting spectrum of conditions with similar vascular ultrasound findings, and suggests that at least in this sample, women may be receiving overtreatment for these presumed uterine AVMs. Close collaboration among gynaecologists and radiologists is needed to interpret the significance of these radiographic images and to determine the appropriate intervention, as women with radiologic findings suspicious of uterine AVM will frequently have retained products of conception.

Background: Women living with HIV (WLWH) experience high rates of anal cancer. Screening using anal cytology, high-resolution anoscopy (HRA) with biopsies, can histologically diagnose anal cancer precursors called high-grade squamous intraepithelial lesions (HSIL). The low specificity of screening using anal cytology results in HRA referral for many WLWH without HSIL. Screening using high-risk human papillomavirus (HR-HPV) may improve specificity., Methods: Two hundred seven WLWH (63% non-Hispanic black) were screened for anal histologic HSIL (hHSIL) using cytology, HRA-guided biopsies, and Xpert HPV. Xpert performance for predicting anal hHSIL was compared with that of cytology. Usng Xpert 5 HPV genotypic results and accompanying cycle thresholds, receiver operator characteristic curve and recursive partitioning analyses were used to create predictive models for hHSIL., Results: The performance of Xpert to predict hHSIL was not different from that of cytology with a sensitivity (Sn) of 89% and specificity (Sp) of 49%. Interpretation of Xpert was modified using genotypic results and receiver operator characteristic curve analysis, which produced a screen with an Sn and Sp of 75% and 84% for hHSIL, respectively. Another reinterpretation of Xpert was created using recursive partitioning and cycle thresholds, which predicted hHSIL with an Sn and Sp of 75% and 86%, respectively. The detection of HPV-16 was highly predictive of hHSIL in all analyses. These modified screening tests would reduce HRA referral in this population by almost half compared with anal cytology., Conclusions: Xpert HPV is an alternative to anal cytology to screen for anal HSIL and can be optimized to reduce the number of unnecessary HRAs performed in WLWH., Competing Interests: G.B.E. was supported by T32 AI007613 (Division of Infectious Weill Cornell Medicine, R. Gulick) and UL1 TR002384 (Weill Cornell Medicine Clinical and Translational Science Center). Funding for this work came from UM1 CA121947 (AIDS Malignancy Consortium, R. Mitsuyasu) and R01 CA163103 (E.Y.C.). N.J. has received honoraria from Antiva and is on Merck and Coadvisory board. R.D.C. has received personal fees from UpToDate, outside the submitted work. S.E.G. has received personal fees from Merck and Co, grants from Antiva and Inovio, and other support from THD America. T.D. has received nonfinancial support from Hologic and personal fees from Roche, BD, Antiva, and TheVax. M.H.E. has advised or participated in educational speaking activities but does not receive honoraria from any companies; his employers have received payment for his time spent for these activities from Papivax, Cynvec, Altum Pharma, Photocure, Becton Dickinson, and PDS Biotechnologies. Rutgers has received grant funding for research-related costs of clinical trials on which M.H.E. has been the overall or local principal investigator from Johnson & Johnson, Pfizer, AstraZeneca, Advaxis, and Inovio; he has also received other support from Photocure, Papivax, Cynvec, PDS, Altum Pharma, and Becton Dickinson, outside the submitted work. E.A.S. has received nonfinancial support from Qiagen and Hologic. J.M.B.-L. has received personal fees from Antiva. J.M.P. has received grants and nonfinancial support from Merck and Co; grants, personal fees, and other support from Vir Biotechnologies, Ubiome, and Antiva Biosciences; personal fees from Janssen Pharmaceuticals, Novan, and Vaccitech; and nonfinancial support from Virion Therapeutics. T.J.W. has received grants and personal fees from GlaxoSmithKline/ViiV Healthcare, outside the submitted work. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Human papillomavirus (HPV)-associated anal and oropharyngeal cancer incidence has increased in recent years among US women. However, trends in incidence and burden (annual number of cases) of noncervical HPV-associated cancers relative to cervical cancer remain unclear. Using the 2001-2017 US cancer statistics dataset, we evaluated contemporary incidence trends and burden (annual number of cases) of HPV-associated cancers among women by anatomic site, race or ethnicity, and age. Overall, cervical cancer incidence plateaued among White women but continued to decline among Black and Hispanic women. Anal cancer incidence surpassed cervical cancer incidence among White women aged 65-74 years of age (8.6 and 8.2 per 100 000 in 2015) and 75 years or older (6.2 and 6.0 per 100 000 in 2014). The noncervical cancer burden (n  =  11 871) surpassed the cervical cancer burden (n  =  11 527) in 2013. Development of efficacious screening strategies for noncervical cancers and continued improvement in cervical cancer prevention are needed to combat HPV-associated cancers among women., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Certain population groups are known to have higher than average anal cancer risk, namely persons living with HIV (PLHIV), men who have sex with men (MSM), women diagnosed with human papillomavirus (HPV)-related gynecological precancerous lesions or cancer, solid organ transplant recipients (SOTRs) and patients with autoimmune diseases. Our aim was to provide robust and comparable estimates of anal cancer burden across these groups. Summary incidence rates (IRs), as cases per 100 000 person-years (py), were calculated by fixed-effects meta-analysis. IRs were 85 (95% confidence interval [CI] = 82-89) for HIV-positive MSM (n = 7 studies; 2 229 234 py), 32 (95% CI = 30-35) for non-MSM male PLHIV (n = 5; 1626 448 py) and 22 (95% CI = 19-24) for female PLHIV (n = 6; 1 472 123 py), with strong variation by age (eg, from 16.8 < 30 years to 107.5 ≥ 60 years for HIV-positive MSM). IR was 19 (95% CI = 10-36) in HIV-negative MSM (n = 2; 48 135 py). Anal cancer IRs were much higher after diagnosis of vulvar (IR = 48 [95% CI = 38-61]; n = 4; 145 147 py) than cervical (9 [95% CI = 8-12]; n = 4; 779 098 py) or vaginal (IR = 10 [95% CI = 3-30]; n = 4; 32 671) cancer, with equivalent disparity after respective precancerous lesions. IR was 13 (95% CI = 12-15) in SOTRs (n = 5; 1 946 206 py), reaching 24.5 and 49.6 for males and females >10 years after transplant. Anal cancer IRs were 10 (95% CI = 5-19), 6 (95% CI = 3-11) and 3 (95% CI = 2-4) for systemic lupus erythematosus, ulcerative colitis and Crohn's disease, respectively. In conclusion, a unifying anal cancer risk scale, based upon comprehensive meta-analysis, can improve prioritization and standardization in anal cancer prevention/research initiatives, which are in their public health infancy., (© 2020 International Agency for Research on Cancer (IARC/WHO); licensed by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.)

Objective: HIV-infected women (WLHIV) have more than 10-fold higher risk for squamous cell cancer of the anus. Experts suggest cytology-based strategies developed for cervical cancer screening may prevent anal cancer by detecting anal cytologic or histological high-grade squamous intraepithelial lesion (hHSIL) for treatment. Currently, there is no consensus on anal-hHSIL screening strategies for WLHIV., Design: Between 2014 and 2016, 276 WLHIV were recruited at 12 US AIDS Malignancy Consortium clinical trials sites to evaluate hHSIL prevalence and (test) screening strategies., Methods: Participants completed detailed questionnaire, underwent anal assessments including high-risk human papillomavirus (hrHPV) testing using hrHPV-Hybrid Capture 2 (HC2) and hrHPV-APTIMA, anal cytology, and concurrent high-resolution anoscopy. Screening test characteristics for predicting hHSIL validated by central review of histologic diagnosis were estimated sensitivity, specificity, positive predictive value, and false-omission rate. Paired analyses compared sensitivity and specificity for hrHPV single tests to anal cytology alone., Results: 83% (229/276) of enrolled WLHIV had complete anal assessment data and were included in this analysis. Mean age was 50, 62% black and 60 (26%) had hHSIL. Anal cyotology (>atypical squamous cells of undetermined significance), hrHPV-HC2, and hrHPV-APTIMA sensitivity estimates were similarly high (83, 77, and 75%, respectively, P values > 0.2). Specificity was higher for both hrHPV-APTIMA and hrHPV-HC2 compared with anal cytology (67 vs. 50%, P < 0.001) and (61 vs. 50%, P = 0.020), respectively., Conclusion: Anal hrHPV testing demonstrated similar sensitivity for anal cytology (>atypical squamous cells of undetermined significance) to predict anal hHSIL. Among tests with similar sensitivity, the specificity was significantly higher for hrHPV-APTIMA and hrHPV-HC2. Thus, anal hrHPV testing may be an important alternative strategy to anal cytology for anal hHSIL screening among WLHIV.

Background: Women living with HIV (WLHIV) have a high risk of developing invasive anal cancer. Anal cancer may be prevented with early detection and treatment of anal histologic high-grade squamous intraepithelial lesions (HSIL). However, there are limited data on the efficacy of anal HSIL treatment in WLHIV., Study Design: We conducted a retrospective study of WLHIV treated for anal HSIL under high-resolution anoscopy (HRA) guidance from January 1, 2007 to December 31, 2017 with at least one post-treatment visit at an urban tertiary care hospital., Results: Forty-five WLHIV women with at least 1 follow-up evaluation after treatment for anal HSIL were identified. The median age was 46 years (range 35-66 years), 63% were African American, 27% were Hispanic/Latino, and 53% were current smokers. The mean absolute CD4 T-cell count was 516 cells/mm; 50% and 24% of the cohort had a history of cervical or vulvar HSIL respectively. The cumulative probability of anal HSIL recurrence was 29% at 12 months, 52% at 24 months, and 79% at 36 months post-treatment., Conclusion: Most WLHIV treated for anal HSIL recurred within 3 years, suggesting need for continued surveillance after treatment. Our data contribute to the information needed to develop effective anal cancer prevention guidelines in WLHIV.

Background: Women living with human immunodeficiency virus (WLHIV) have disproportionately high rates of squamous cell carcinoma of the anus compared with the general population of women. Anal high-grade squamous intraepithelial lesions (HSILs) precede anal cancer, and accurate studies of HSIL prevalence among WLHIV in the United States are lacking., Methods: The AIDS Malignancy Consortium 084 study was a multicenter national trial to evaluate the prevalence of and risk factors for anal HSIL in a US cohort. Eligible participants were WLHIV aged ≥18 years with no history of anal HSIL. Study participants had an examination including collection of cervical/vaginal and anal specimens, followed by high-resolution anoscopy with biopsy., Results: We enrolled 256 women with evaluable anal pathology. The mean age was 49.4 years, 64% women were non-Hispanic black, 67% were former or current smokers, and 56% reported ever having anal sex with a man. The median CD4 T-cell count was 664 cells/μL. The prevalence of anal histologic HSIL (hHSIL) was 27% (95% confidence interval [CI], 22%-33%). There was a strong concordance (240/254) between local and consensus pathologists for hHSIL vs less than hHSIL (κ = 0.86 [95% CI, .79-.93]). Current CD4 count of ≤200 cells/μL was the strongest predictor of consensus anal hHSIL diagnosis (adjusted odds ratio [aOR], 10.34 [95% CI, 3.47-30.87]). History of anoreceptive intercourse was also associated with hHSIL (aOR, 2.44 [95% CI, 1.22-4.76])., Conclusions: The prevalence of anal hHSIL in WLHIV in the United States was 27% in this study where all participants received high-resolution anoscopy and biopsy., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: There are no uniform screening recommendations for anal cancer. Medical practice guidelines are now available on the use of Digital Anal Rectal Examinations (DARE) for the detection of anal cancer; however, because screening can result in more harm than benefit, our objective was to assess the evidence for use of DARE as a public health screening tool., Materials and Methods: We conducted a current critical appraisal of anal cancer literature using World Health Organization criteria for assessing the potential utility of a public health screening program., Results: Digital Anal Rectal Examination satisfies most, but not all, World Health Organization criteria for a public health program that seeks to detect early invasive anal cancer in populations at high risk for anal cancer, most notably HIV-positive men who have sex with men; however, DARE is not appropriate when facilities for treatment are nonexistent. In addition, there are insufficient data on DARE sensitivity and specificity., Conclusions: The mildly invasive nature of DARE, limited likelihood of adverse procedure-related events, cost-effectiveness and patient acceptability, as well as wide availability of DARE support consideration of its integration into screening for populations at high risk of anal cancer, especially HIV-positive men who have sex with men.

The aims of this study were to: 1) determine prevalence of anogenital and oral HPV, 2) determine concordance between HPV at anal, perianal, scrotal/penile, and oral sites; and 3) describe factors associated with anogenital HPV types targeted by the 9-valent vaccine. Data were collected from 2012 to 2015 among men who have sex with men 18-26 years of age enrolled in a vaccine trial (N = 145). Penile/scrotal, perianal, anal, and oral samples were tested for 61 HPV types. Logistic regression was used to identify factors associated with types in the 9-valent vaccine. Participants' mean age was 23.0 years, 55.2% were African-American, and 26.2% were Hispanic; 93% had anal, 40% penile, and 6% oral HPV. Among those with anogenital infection, 18% had HPV16. Concordance was low between anogenital and oral sites. Factors independently associated with a 9-valent vaccine-type HPV were: race (African-American vs. White, OR=2.67, 95% CI=1.11-6.42), current smoking (yes vs. no, OR=2.37, 95% CI=1.03-5.48), and number of recent receptive anal sex partners (2+ vs. 0, OR=3.47, 95% CI=1.16-10.4). Most MSM were not infected with HPV16 or HPV18, suggesting that they may still benefit from HPV vaccination, but anogenital HPV was very common, highlighting the importance of vaccinating men before sexual initiation. CLINICAL TRIAL NUMBER: NCT01209325., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of the study was to develop recommended techniques and quality assurance metrics for the practice of Digital Anal Rectal Examination (DARE)., Materials and Methods: The International Anal Neoplasia Society undertook a literature review and, using the AGREE II technique, developed guidelines for performing DARE., Results: A consensus was formed regarding the optimum conditions and characteristics of DARE. Several Quality Assurance metrics were developed., Conclusions: Digital Anal Rectal Examination is a cheap and potentially universally available technique, which has the potential to facilitate the early diagnosis of anal cancers, when they are most amenable to treatment. These guidelines provide a basis for teaching the technique and may be used as for evaluation research.

Purpose: To determine the feasibility, safety, and tolerability of concomitant chemoradiotherapy administered at standard doses in HIV-infected women with locally-advanced cervical cancer (LACC) receiving antiretroviral therapy (ART)., Patients and Methods: Eligible participants had HIV infection and untreated, histologically-confirmed, invasive carcinoma of the uterine cervix, FIGO stages IB2, IIA (if tumor >4 cm), IIB, IIIA, IIIB, or IVA and met standard eligibility criteria. Subjects were prescribed 41.4-45 Gy external beam radiation therapy followed by high dose rate brachytherapy concomitant with up to six weekly doses of cisplatin 40 mg/m2 and were followed for 12 months., Results: Sixty-four women were screened at two sites in sub-Saharan Africa, of whom 40 eligible participants were enrolled, for a screening ratio of 1.60. Of the 38 eligible participants who initiated study treatment, 31 (82%) completed treatment. By the 12-month follow-up visit, 7 women had died of disease and 29 of 31 (94%) returned for follow-up. One-year progression-free survival was 76.3% (95% CI, 59.4-86.9%), and did not significantly differ according to stage at entry (p = 0.581). Participant-reported adherence to ART was high; by 12 months, 93% of participants had an undetectable viral load. The most common grade 3 or 4 adverse event was decreased lymphocyte count that affected all treated participants. Non-hematologic serious adverse events were similar to those observed in women with LACC without HIV infection., Conclusions: The majority of HIV-infected women with LACC can complete concomitant chemoradiotherapy with the same cisplatin dose used in HIV-uninfected women with comparable tolerability and high ART adherence while on treatment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Anal high-grade squamous intraepithelial lesions (HSILs) ablation may reduce the incidence of invasive cancer, but few data exist on treatment efficacy and natural regression without treatment., Methods: An open-label, randomized, multisite clinical trial of human immunodeficiency virus (HIV)-infected adults aged ≥27 years with 1-3 biopsy-proven anal HSILs (index HSILs) without prior history of HSIL treatment with infrared coagulation (IRC). Participants were randomized 1:1 to HSIL ablation with IRC (treatment) or no treatment (active monitoring [AM]). Participants were followed every 3 months with high-resolution anoscopy. Treatment participants underwent anal biopsies of suspected new or recurrent HSILs. The AM participants underwent biopsies only at month 12. The primary end point was complete clearance of index HSIL at month 12., Results: We randomized 120 participants. Complete index HSIL clearance occurred more frequently in the treatment group than in the AM (62% vs 30%; risk difference, 32%; 95% confidence interval [CI], 13%-48%; P < .001). Complete or partial clearance (clearance of ≥1 index HSIL) occurred more commonly in the treatment group (82% vs 47%; risk difference, 35%; 95% CI, 16%-50%; P < .001). Having a single index lesion, compared with having 2-3 lesions, was significantly associated with complete clearance (relative risk, 1.96; 95% CI, 1.22-3.10). The most common adverse events related to treatment were mild or moderate anal pain and bleeding. No serious adverse events were deemed related to treatment or study participation., Conclusion: IRC ablation of anal HSILs results in more clearance of HSILs than observation alone., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at disproportionately high risk for anal cancer. There is no definitive approach to the management of high-grade squamous intraepithelial lesions (HSIL), which are precursors of anal cancer, and evidence suggests that posttreatment adjuvant quadrivalent human papillomavirus (qHPV) vaccination improves HSIL treatment effectiveness. The objectives of this study were to evaluate the optimal HSIL management strategy with respect to clinical effectiveness and cost-effectiveness and to identify the optimal age for initiating HSIL management., Methods: A decision analytic model of the natural history of anal carcinoma and HSIL management strategies was constructed for HIV-positive MSM who were 27 years old or older. The model was informed by the Surveillance, Epidemiology, and End Results-Medicare database and published studies. Outcomes included the lifetime cost, life expectancy, quality-adjusted life expectancy, cumulative risk of cancer and cancer-related deaths, and cost-effectiveness from a societal perspective., Results: Active monitoring was the most effective approach in patients 29 years or younger; thereafter, HSIL treatment plus adjuvant qHPV vaccination became most effective. When cost-effectiveness was considered (ie, an incremental cost-effectiveness ratio [ICER] < $100,000/quality-adjusted life-year), do nothing was cost-effective until the age of 38 years, and HSIL treatment plus adjuvant qHPV vaccination was cost-effective beyond the age of 38 years (95% confidence interval, 34-43 years). The ICER decreased as the age at HSIL management increased. Outcomes were sensitive to the rate of HSIL regression or progression and the cost of high-resolution anoscopy and biopsy., Conclusions: The management of HSIL in HIV-positive MSM who are 38 years old or older with treatment plus adjuvant qHPV vaccination is likely to be cost-effective. The conservative approach of no treatment is likely to be cost-effective in younger patients. Cancer 2017;123:4709-4719. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Objectives: The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. Working group 3 defined colposcopy procedure guidelines for minimum and comprehensive colposcopy practice and evaluated the use of colposcopy adjuncts., Materials and Methods: The working group performed a systematic literature review to identify best practices in colposcopy methodology and to evaluate the use of available colposcopy adjuncts. The literature provided little evidence to support specific elements of the procedure. The working group, therefore, implemented a national survey of current and recent ASCCP members to evaluate common elements of the colposcopy examination. The findings of this survey were modified by expert consensus from the ASCCP Colposcopy Standards Committee members to create guidelines for performing colposcopy. The draft recommendations were posted online for public comment and presented at an open session of the International Federation for Cervical Pathology and Colposcopy 2017 World Congress for further comment. All comments were considered in the development of final recommendations., Results: Minimum and comprehensive colposcopy practice guidelines were developed. These guidelines represent recommended practice in all parts of the examination including the following: precolposcopy evaluation, performing the procedure, documentation of findings, biopsy practice, and postprocedure follow-up., Conclusions: These guidelines are intended to serve as a guide to standardize colposcopy across the United States.

The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of colposcopy and directed biopsy for cervical cancer prevention in the United States (US). The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. An extensive literature review was conducted and supplemented by a systematic review and meta-analysis of unpublished data. In addition, a survey of practicing colposcopists was conducted to assess current colposcopy practice in the US. Recommendations were approved by the working group members, and the final revisions were made based on comments received from the public. The recommendations cover terminology, risk-based colposcopy, colposcopy procedures, and colposcopy adjuncts. The ASCCP Colposcopy Standards recommendations are an important step toward raising the standard of colposcopy services delivered to women in the US. Because cervical cancer screening programs are currently undergoing important changes that may affect colposcopy performance, updates to some of the current recommendations may be necessary in the future.

Importance: Outcomes of treating high-grade squamous intraepithelial lesions (HSIL), a precursor to anal cancer, remain uncertain. Emerging evidence shows that post HSIL treatment adjuvant quadrivalent human papillomavirus (qHPV) vaccination improves the effectiveness of treatment. However, no recommendations exist regarding the use of qHPV vaccine as an adjuvant form of therapy. Our objective was to determine whether post-treatment adjuvant vaccination should be adopted in HIV-infected MSM (individuals at highest risk for anal cancer) on the basis of cost-effectiveness determined using existing evidence or whether future research is needed., Methods: We developed a Markov (state-transition) cohort model to assess the cost-effectiveness of post-treatment adjuvant HPV vaccination of 27years or older HIV-infected MSM. We first estimated cost-effectiveness and then performed value-of-information (VOI) analysis to determine whether future research is required by estimating the expected value of perfect information (EVPI). We also estimated expected value of partial perfect information (EVPPI) to determine what new evidences should have highest priority., Results: With the incremental cost-effectiveness ratio (ICER) of $71,937/QALY, "treatment plus vaccination" was the most cost-effective HSIL management strategy using the willingness-to-pay threshold of 100,000/QALY. We found that population-level EVPI for conducting future clinical research evaluating HSIL management approaches was US$12 million (range $6-$20 million). The EVPPI associated with adjuvant qHPV vaccination efficacy estimated in terms of hazards of decreasing HSIL recurrence was $0 implying that additional data from a future study evaluating efficacy of adjuvant qHPV vaccination will not change our policy conclusion that "treatment plus vaccination" was cost-effective. Both the ICER and EVPI were sensitive to HSIL treatment compliance., Conclusion: Post-treatment adjuvant qHPV vaccination in HIV-infected MSM aged 27 or above is likely to be cost-effective. Use of adjuvant qHPV vaccination could be considered as a potential strategy to reduce rising anal cancer burden among these high-risk individuals., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The epidemiology of anal cancer in the U.S. has changed over the past 3 decades. During this period the incidence of anal cancer has increased among both men and women. Of note, women with a history of anogenital HPV infection are at higher risk than the general population for anal cancer. The increased risk ranged from increased incidence rate ratios ranging from 1.82 to 6.3 in women with a history of cervical cancer, to 4.2-16.4 in women with a history of prior cervical intraepithelial neoplasia 3 (CIN 3). In addition, studies describing screening women with a previous history of anogential HPV infection (including CIN 3) for anal HPV and anal pre-cancers demonstrate that the prevalence of anal HPV is measureable in this population. The prevalence of anal high grade squamous intraepithelial lesions (HSIL) in this population was relatively low, which may have been related to the fact that many of these studies had insufficient samples, and the numbers of patients undergoing HRA remain low. Future studies evaluating anal cancer screening strategies in this high-risk group are needed.

Objective: The aim of the study was to assess whether HIV-positive (HIV+) women aged 30 years and older with concurrent normal cervical cytology and undetectable cervical HPV have a low 3-year risk of developing cervical intraepithelial neoplasia grade 2 or higher (CIN 2+) in a clinical setting., Materials and Methods: We conducted a retrospective chart review of HIV+ women aged 30 years and older at a single institution with normal cervical cytology and concurrent human papillomavirus (HPV) testing between November 2008 and December 2010. The participants were stratified by initial HPV testing results and followed to either the study end point (CIN 2+) or until the last cervical cytology or colposcopy before January 2015. Kaplan-Meier survival curves were used to analyze CIN 2+ diagnosis for follow-up with log-rank testing of the null hypothesis. Cox proportional hazard regression was performed to calculate crude and adjusted hazard ratios controlling for ethnicity and CD4 levels., Results: We identified 325 HIV+ women with normal cytology and follow-up; 66 (20%) of these women had detectable HPV. The cumulative diagnosis of CIN 2+ at 4 years was significantly lower in the HPV-negative cohort compared with the HPV-positive cohort (1.4%, 95% CI = 0.3%-4.6% vs 14.5%, 95% CI = 5.8%-27.1%), respectively; the median duration to CIN 2+ diagnosis was longer in the HPV-negative cohort compared with the HPV-positive cohort (4.2 years vs 1.5 years, respectively, p < .02)., Conclusions: HIV+ women aged 30 years and older with concurrent normal cervical cytology and undetectable cervical HPV have a low 3-year risk of subsequent diagnosis of CIN 2+. The study validates the recently updated US recommendations for the use of co-testing in screening HIV+ women.

Objectives: To define minimum standards for provision of services and clinical practice in the investigation of anal cancer precursors., Methods: After initial face to face meetings of experts at the International Papillomavirus meeting in Lisbon, September 17 to 21, 2015, a first version was drafted and sent to key stakeholders. A complete draft was reviewed by the Board of the International Anal Neoplasia Society (IANS) and uploaded to the IANS Web site for all members to provide comments. The final draft was ratified by the IANS Board on June 22, 2016., Results: The essential components of a satisfactory high-resolution anoscopy (HRA) were defined. Minimum standards of service provision, basic competencies for clinicians, and standardized descriptors were established. Quality assurance metrics proposed for practitioners included a minimum of 50 HRAs per year and identifying 20 cases or more of anal high-grade squamous intraepithelial lesions (HSILs). Technically unsatisfactory anal cytological samples at first attempt in high-risk populations should occur in less than 5% of cases. Where cytological HSIL has been found, histological HSIL should be identified in ≥ 90% of cases. Duration of HRA should be less than 15 minutes in greater than 90% of cases. Problematic pain or bleeding should be systematically collected and reported by 10% or lesser of patients., Conclusions: These guidelines propose initial minimum competencies for the clinical practice of HRA, against which professionals can judge themselves and providers can evaluate the effectiveness of training. Once standards have been agreed upon and validated, it may be possible to develop certification methods for individual practitioners and accreditation of sites.

The incidence of anal cancer is increasing. High risk populations include HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive women and heterosexual men and women with a history of cervical cancer. HPV has been detected in over 90% of anal cancers. HPV16 is the most common genotype detected in about 70% of anal cancers. The quadrivalent HPV (qHPV) vaccine has been demonstrated to prevent vaccine associated persistent anal HPV infections as well as anal intraepithelial neoplasia grades 2-3 (AIN2+) in young MSM not previously infected. A retrospective analysis also suggests that qHPV vaccination of older MSM treated for AIN2+ may significantly decrease the risk of recurrence of the AIN2+. The HPV types detected in anal cancer are included in the 9-valent vaccine. Thus, the 9-valent HPV vaccine, when administered to boys and girls prior to the onset of sexual activity, should effectively prevent anal cancer.

Background: Infection with the human immunodeficiency virus (HIV) remains associated with a greater risk of anal cancer, despite widespread use of combination antiretroviral therapy. Evidence concerning the acceptability of anal cancer screening gives little attention to women. Because HIV-infected women have a high prevalence of depression and history of sexual trauma, understanding acceptability among this group is critical., Purpose: We sought to assess barriers and motivators to participation in anal cancer screening research among a racial/ethnically diverse HIV-infected female population., Methods: We conducted a survey based on the Health Belief Model to identify characteristics of women willing to participate in anal cancer screening research (n = 200). Bivariate analyses examined associations between willingness to participate and sociodemographics, clinical characteristics, and health beliefs. Logistic regression modeled willingness to participate in research., Main Findings: Of the women who participated, 37% screened positive for depression, 43% reported a high trauma history, and 36% screened positive for posttraumatic stress disorder. Overall, 65% reported willingness to participate in research. Those likely to participate were older, reported intravenous drug use as their HIV risk factor, and had a history of prior high-resolution anoscopy (HRA) compared with those unwilling to participate. The most commonly reported barrier to anal Pap testing was fear of pain. In adjusted analyses, a lack of fear of pain and prior experience with HRA significantly predicted willingness to participate., Conclusions: Findings suggest that, to increase participation in anal Pap and HRA-related research for HIV-infected women, a single approach may not be adequate. Rather, we must harness patients' previous experiences and address psychosocial and financial concerns to overcome barriers to participation., (Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to systematically review the findings of publications addressing the epidemiology of anal human papillomavirus (HPV) infection, anal intraepithelial neoplasia, and anal cancer in women. We conducted a systematic review among publications published from Jan. 1, 1997, to Sept. 30, 2013, to limit to publications from the combined antiretroviral therapy era. Three searches were performed of the National Library of Medicine PubMed database using the following search terms: women and anal HPV, women anal intraepithelial neoplasia, and women and anal cancer. Publications were included in the review if they addressed any of the following outcomes: (1) prevalence, incidence, or clearance of anal HPV infection, (2) prevalence of anal cytological or histological neoplastic abnormalities, or (3) incidence or risk of anal cancer. Thirty-seven publications addressing anal HPV infection and anal cytology remained after applying selection criteria, and 23 anal cancer publications met the selection criteria. Among HIV-positive women, the prevalence of high-risk (HR)-HPV in the anus was 16-85%. Among HIV-negative women, the prevalence of anal HR-HPV infection ranged from 4% to 86%. The prevalence of anal HR-HPV in HIV-negative women with HPV-related pathology of the vulva, vagina, and cervix compared with women with no known HPV-related pathology, varied from 23% to 86% and from 5% to 22%, respectively. Histological anal high-grade squamous intraepithelial lesions (anal intraepithelial neoplasia 2 or greater) was found in 3-26% of the women living with HIV, 0-9% among women with lower genital tract pathology, and 0-3% for women who are HIV negative without known lower genital tract pathology. The incidence of anal cancer among HIV-infected women ranged from 3.9 to 30 per 100,000. Among women with a history of cervical cancer or cervical intraepithelial neoplasia 3, the incidence rates of anal cancer ranged from 0.8 to 63.8 per 100,000 person-years, and in the general population, the incidence rates ranged from 0.55 to 2.4 per 100,000 person-years. This review provides evidence that anal HPV infection and dysplasia are common in women, especially in those who are HIV positive or have a history of HPV-related lower genital tract pathology. The incidence of anal cancer continues to grow in all women, especially those living with HIV, despite the widespread use of combined antiretroviral therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The incidence of anal cancer is higher in women than men in the general population and has been increasing for several decades. Similar to cervical cancer, most anal cancers are associated with human papillomavirus (HPV), and it is believed that anal cancers are preceded by anal high-grade squamous intraepithelial lesions (HSIL). Our goals were to summarize the literature on anal cancer, HSIL, and HPV infection in women and to provide screening recommendations in women., Methods: A group of experts convened by the American Society for Colposcopy and Cervical Pathology and the International Anal Neoplasia Society reviewed the literature on anal HPV infection, anal SIL, and anal cancer in women., Results: Anal HPV infection is common in women but is relatively transient in most. The risk of anal HSIL and cancer varies considerably by risk group, with human immunodeficiency virus-infected women and those with a history of lower genital tract neoplasia at highest risk compared with the general population., Conclusions: While there are no data yet to demonstrate that identification and treatment of anal HSIL leads to reduced risk of anal cancer, women in groups at the highest risk should be queried for anal cancer symptoms and required to have digital anorectal examinations to detect anal cancers. Human immunodeficiency virus-infected women and women with lower genital tract neoplasia may be considered for screening with anal cytology with triage to treatment if HSIL is diagnosed. Healthy women with no known risk factors or anal cancer symptoms do not need to be routinely screened for anal cancer or anal HSIL.

Purpose: High-grade anal intraepithelial neoplasia (HGAIN) is the precursor lesion to invasive anal cancer. Human papillomavirus (HPV) vaccination holds great promise for preventing anal cancer., Methods: We examined 235 HIV-1-infected men screening for participation in a multisite clinical trial of a quadrivalent HPV vaccine. All participants had anal swabs obtained for HPV testing and cytology and high-resolution anoscopy with biopsies of visible lesions to assess for HGAIN., Results: HPV types 16 and 18 were detected in 23% and 10%, respectively; abnormal anal cytology was found in 56% and HGAIN in 30%. HGAIN prevalence was significantly higher in those with HPV16 detection compared to those without (38% vs 17%; P = .01). Use of antiretroviral therapy and nadir and current CD4+ cell count were not associated with abnormal anal cytology or HGAIN., Conclusion: HGAIN is highly prevalent in HIV-infected men. Further studies are needed on treatment and prevention of HGAIN.

Objective: To evaluate the safety and efficacy of topical cidofovir for treatment of high-grade squamous perianal intraepithelial neoplasia (PAIN) and vulvar intraepithelial neoplasia (VIN) lesions in HIV-positive individuals., Design: Phase IIa prospective multicenter trial conducted at eight clinical sites through the AIDS Malignancy Consortium., Methods: : HIV-positive patients with biopsy-proven high-grade PAIN that was at least 3 cm were enrolled. PAIN biopsy specimens were assessed for human papillomavirus (HPV) using PCR and type-specific HPV probing. Participants applied 1% topical cidofovir to PAIN and VIN (if present) for six 2-week cycles. Results were designated as complete response (CR), partial response (PR) (>50% reduction in size), stable disease, or progressive disease (PD)., Results: Twenty-four men and nine women (eight with high-grade VIN as well) were enrolled. Mean age was 44 years and mean CD4 cell count was 412 cells/μl. HPV DNA (most commonly HPV16) was detected in all pretreatment study specimens. Twenty six (79%) participants completed treatment per protocol: CR, five (15%); PR, 12 (36%), stable disease, seven (21%); PD, two (6%) (one with a superficially invasive cancer and one with new area of high-grade PAIN). Treatment was well tolerated with most common adverse events being mild to moderate affecting lesional skin: pain/burning/irritation (25 patients) and ulceration (13 patients)., Conclusion: Topical cidofovir had 51% efficacy in the short-term treatment of high-grade PAIN and VIN with acceptable toxicity in HIV-positive individuals. Randomized control studies with more prolonged treatment courses and longer follow-up to assess the durability of the response are needed.