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The ability to experience pleasurable sexual activity is important for human health. Receptive anal intercourse (RAI) is a common, though frequently stigmatized, pleasurable sexual activity. Little is known about how diseases of the colon, rectum, and anus and their treatments affect RAI. Engaging in RAI with gastrointestinal disease can be difficult due to the unpredictability of symptoms and treatment-related toxic effects. Patients might experience sphincter hypertonicity, gastrointestinal symptom-specific anxiety, altered pelvic blood flow from structural disorders, decreased sensation from cancer-directed therapies or body image issues from stoma creation. These can result in problematic RAI - encompassing anodyspareunia (painful RAI), arousal dysfunction, orgasm dysfunction and decreased sexual desire. Therapeutic strategies for problematic RAI in patients living with gastrointestinal diseases and/or treatment-related dysfunction include pelvic floor muscle strengthening and stretching, psychological interventions, and restorative devices. Providing health-care professionals with a framework to discuss pleasurable RAI and diagnose problematic RAI can help improve patient outcomes. Normalizing RAI, affirming pleasure from RAI and acknowledging that the gastrointestinal system is involved in sexual pleasure, sexual function and sexual health will help transform the scientific paradigm of sexual health to one that is more just and equitable., (© 2024. Springer Nature Limited.)

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: International data on anogenital HPV infection incidence among men are limited., Methods: Incidence of incident-persistent (IP) anogenital HPV infections was evaluated among 295 men who have sex with men (MSM) and 1576 heterosexual men (HM) aged 16-27 years in the placebo arm of a global, multicenter 4-valent (4v) HPV vaccine trial. We estimated IP incidence (penile/scrotal, perineal/perianal, anal) for 4vHPV and 9-valent (9v) HPV vaccine types and cumulative IP incidence over 36 months., Results: IP infection incidence per 100 person-years (95% CI) among HM for 4vHPV and 9vHPV types was 4.1 (3.5-4.9) and 6.8 (5.9-7.6) at penile/scrotal, and 1.2 (.8-1.6) and 1.9 (1.5-2.4) at perineal/perianal sites, respectively; and among MSM, IP infection incidence was 2.3 (1.3-3.8) and 3.2 (2.0-4.9) at penile/scrotal, 6.8 (4.9-9.2) and 9.0 (6.9-11.6) at perineal/perianal, and 12.0 (9.4-15.1) and 16.8 (13.7-20.2) at anal sites, respectively. Cumulative IP incidence over 36 months (excluding anal canal; any 9vHPV type) was higher among MSM versus HM (24.1% vs 18.4%)., Conclusions: A substantial proportion of unvaccinated men of catch-up vaccination age developed IP 9vHPV-related infections. Gender-neutral vaccination could decrease male HPV infection, contribute to herd protection, and reduce disease burden. Clinical Trials Registration. NCT00090285., Competing Interests: Potential conflicts of interest. A. R. G. reports receipt of support in the form of medical writing for the current manuscript, grants, and consulting fees from Merck Sharp & Dohme LLC. J. M. P. reports receipt of consulting fees from Merck Sharp & Dohme, LLC, Vir Biotechnologies, Antiva Biosciences, and Roche Diagnostics; has received payment from Merck Sharp & Dohme LLC, for lectures, presentations, speakers’ bureaus, and manuscript writing or educational events; is an honorary board member of the International Papillomavirus Society; and holds stock or stock options in Virion Therapeutics. S. G. has received grants from Inovio and Franz Viral Technologies; consulting fees from THD America; and payment or honoraria from Merck Sharp & Dohme, LLC, for speakers’ bureaus. S. G. and J. E. T. have received support from Merck Sharp & Dohme, LLC, for the present manuscript. A. L., B. D., A. S., C. V., and J. E. T. are employees of Merck Sharp & Dohme, LLC. A. L., B. D., A. S., and J. E. T. hold stock in Merck & Co, Inc, Rahway, NJ, USA. 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.)

The risk for acquiring human papillomavirus (HPV) infections and associated diseases is lifelong. An important part of prophylactic HPV vaccine development is durable protection against infection and disease. With comprehensive long-term follow-up (LTFU) in adolescents, men, and women, the quadrivalent HPV (qHPV) vaccine demonstrated durable effectiveness, immunogenicity, and safety, with almost no breakthrough disease. Those who received a placebo during initial trials were offered the qHPV vaccine at study conclusion and continued to be followed in LTFU extensions. In this catch-up vaccination group, LTFU demonstrated protection even in individuals with current or prior HPV infection after approximately 3 years. The initial efficacy and durable long-term effectiveness of the qHPV vaccine have already translated to a real-world reduction in cancer and cancer precursors. To date, there is no evidence of waning protection; evidence suggests that vaccination ultimately provides strong protection against future disease, with effective prophylaxis even among those with past infections.

Background: Targeted ablation of anal canal high-grade dysplasia results in high recurrence over time. Circumferential radiofrequency ablation might decrease recurrence., Objective: This study aimed to determine the safety and efficacy of circumferential radiofrequency ablation for anal high-grade dysplasia., Design: This was a dual-center, prospective trial of circumferential radiofrequency ablation with a 1-year follow-up with longer follow-up data abstracted from medical records of study patients returning after trial for surveillance. Ten participants from the identically conducted pilot circumferential radiofrequency ablation trial were included to improve sample size for longer-term analysis., Settings: This study included 3 surgeons at 2 sites., Patients: The study included 51 patients undergoing circumferential radiofrequency ablation for anal canal high-grade dysplasia., Intervention: Circumferential radiofrequency ablation of anal canal high-grade dysplasia and targeted radiofrequency ablation of recurrence., Main Outcome Measures: The primary outcome measures were circumferential radiofrequency ablation efficacy and associated morbidity., Results: Fifty-one participants underwent circumferential radiofrequency ablation but 48 participants returned for 1 or more postprocedure high-resolution anoscopy and were evaluable. The mean age of participants was 43 years, most were male (94%), 33% were living with HIV, and 58% had 3 or more high-grade dysplasias treated. Sixty percent had no recurrence, whereas 19% had 1 recurrence, 15% had 2 recurrences, and 6% had 3 recurrences. Most recurrences (66%) developed within the first 6 months. Kaplan-Meier probability of recurrence combining both series was 19% at 3 months, 30% at 6 months, and approximately 40% after 6 months out to 30 months. Most common morbidities were pain (85.4%) lasting for a median of 21 (range, 4-91) days and bleeding (91%) lasting for a median of 21 (range, 5-87) days. Of those with pain and bleeding, 65% and 85%, respectively, described it as mild. No patients developed fistulas, stricture, or incontinence. No serious adverse events related to circumferential radiofrequency ablation occurred. Having a previous recurrence was the only significant predictor of a subsequent recurrence (HR, 28.53) for recurrence at 9 months or before., Limitations: Enrollment ended prematurely, 10 participants from the pilot study were combined to increase the sample size, and longer-term follow-up was collected retrospectively were the limitations of this study., Conclusions: Circumferential radiofrequency ablation has improved efficacy over targeted ablation but with increased pain and bleeding. See Video Abstract at http://links.lww.com/DCR/B973 ., Estudio Prospectivo Bicntrico Sobre La Ablacin Por Radiofrecuencia Circunferencial De Lesiones Anales Intraepiteliales Escamosas De Alto Grado Demostrando Mayor Eficacia a Largo Plazo Con Relacin a Controles Histricos De Ablacin Dirigida: ANTECEDENTES:La ablación dirigida de la displasia de alto grado en el canal anal proporciona como resultados una alta recidiva a largo plazo. La ablación por radiofrecuencia circunferencial podría disminuir la reincidencia.OBJETIVO:Determinar la seguridad y eficacia de la ablación por radiofrecuencia circunferencial para la displasia anal de alto grado.DISEÑO:Estudio prospectivo bicéntrico de ablación por radiofrecuencia circunferencial con un seguimiento de 1 año, en base al monitoreo prolongado de datos, obtenidos de los registros medicos, de todos los pacientes incluidos en el estudio y que fueron controlados clinicamente. Diez participantes del estudio piloto de ablación por radiofrecuencia circunferencial realizada de manera idéntica, se combinaron para mejorar el análisis del tamaño de la muestra a largo plazo.PACIENTES:Se incluyeron 51 pacientes sometidos a la ablación por radiofrecuencia circunferencial de una lesion displásica de alto grado en el canal anal.AJUSTES:Tres cirujanos en 2 centros.INTERVENCIÓN:Ablación por radiofrecuencia circunferencial de la displasia de alto grado en el canal anal y ablación por radiofrecuencia dirigida de la recidiva.PRINCIPALES MEDIDAS DE RESULTADOS:Las medidas primarias fueron la eficacia de la ablación por radiofrecuencia circunferencial y la morbilidad asociada.RESULTADOS:Cincuenta y un participantes se sometieron a la ablación por radiofrecuencia circunferencial, de los cuales, 48 regresaron para ser evaluados con ≥1 anuscopias de alta resolución, después del procedimiento. La edad media de los participantes fue de 43 años, en su mayoría hombres (94%), el 33% eran portadores de VIH y el 58% tenía ≥3 lesiones displásicas de alto grado tratadas. El sesenta por ciento no tuvo recidiva, mientras que el 19%, 15% y 6% tuvieron 1, 2 o 3 recidivas. La mayoría de las recaídas (66%) se desarrollaron dentro de los primeros 6 meses. La probabilidad de recurrencia de Kaplan-Meier combinando ambas series fue del 19 % a los 3 meses, del 30 % a los 6 meses y aproximadamente del 40 % entre los 6 y 30 meses. Los indicadores de morbilidad más frecuentes fueron, el dolor (85,4%) con una mediana de duración de 21 días (rango, 4-91) y sangrado (91%) con una mediana de duración de 21días (rango, 5-87). Aquellos pacientes con dolor (65%) y sangrado (85%) respectivamente, los describieron como leves. Ningún paciente desarrolló fístula, estenosis o incontinencia. No se produjeron eventos adversos graves relacionados con la ablación por radiofrecuencia circunferencial. Tener una recurrencia previa fue el único factor predictivo importante de una recidiva ulterior (RH 28,53) en casos de recaída a los 9 meses o antes.LIMITACIONES:Como el registro finalizó prematuramente, se agregaron 10 participantes del estudio piloto para aumentar el tamaño de la muestra. El seguimiento a largo plazo fué recopilado retrospectivamente.CONCLUSIONES:La ablación por radiofrecuencia circunferencial ha mejorado la eficacia sobre la ablación dirigida pero con dolor y sangrado mas importantes. Consulte Video Resumen en http://links.lww.com/DCR/B973 . ( Traducción-Dr. Xavier Delgadillo )., (Copyright © The ASCRS 2022.)

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.)

Background: In men, the incidence of human papillomavirus (HPV)-related cancer is rising, but data regarding male HPV infection and seroprevalence are available from only a few countries., Methods: This analysis of a global HPV vaccine trial evaluated baseline data from 1399 human immunodeficiency virus-negative heterosexual men (HM) and men who have sex with men (MSM). Key objectives included assessment of HPV prevalence and risk factors for seropositivity to 9-valent HPV (9vHPV) vaccine types (6, 11, 16, 18, 31, 33, 45, 52, and 58), and concordance between seropositivity and prevalent HPV type., Results: Overall, 455 of 3463 HM (13.1%) and 228 of 602 MSM (37.9%) were HPV DNA positive for any 9vHPV vaccine type at baseline. Infection prevalence and seroprevalence (≥1 9vHPV vaccine type) were 13.2% and 8.1%, respectively, among 333 HM from Europe, and 37.9% and 29.9%, respectively, among 335 MSM from Europe or North America. Among men with baseline infection, MSM had higher seroprevalence for concordant HPV types (39.5% vs 10.8% in HM). The seropositivity risk (irrespective of baseline infection status) was higher among MSM versus HM (age-adjusted odds ratio, 3.0 [95% confidence interval, 2.4-6.4]). Among MSM, statistically significant seropositivity risk factors included younger age at sexual debut, higher number of receptive anal sex partners, and less frequent condom use. No factors assessed were associated with seropositivity in HM., Conclusions: Higher proportions of MSM than HM were HPV DNA positive and seropositive, and concordance between HPV DNA positivity and seropositivity, a potential marker of true infection versus carriage, was higher in MSM. Most MSM and HM were seronegative for all 9vHPV vaccine types, suggesting the potential benefit of catch-up vaccination after sexual debut.Clinical Trials Registration. NCT00090285., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: The quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in a randomised, placebo-controlled study in men aged 16-26 years. We assessed the incidences of external genital warts related to HPV6 or 11, and external genital lesions and anal dysplasia related to HPV6, 11, 16, or 18, over 10 years of follow-up., Methods: The 3-year base study was an international, multicentre, double-blind, randomised, placebo-controlled trial done at 71 sites in 18 countries. Eligible participants were heterosexual men (aged 16-23 years) or men who have sex with men (MSM; aged 16-26 years). Men who had clinically detectable anogenital warts or genital lesions at screening that were suggestive of infection with non-HPV sexually transmitted diseases, or who had a history of such findings, were excluded. Eligible participants were randomly assigned (1:1) to receive three doses of either quadrivalent HPV vaccine or placebo on day 1, month 2, and month 6, administered as a 0·5-mL injection into the deltoid muscle. The 7-year, open-label, long-term follow-up extension study was done at 46 centres in 16 countries. Participants who received one or more doses of the quadrivalent HPV vaccine in the base study were eligible for enrolment into the long-term follow-up study (early vaccination group). Placebo recipients were offered the three-dose quadrivalent HPV vaccine at the end of the base study; those who received one or more quadrivalent HPV vaccine doses were eligible for enrolment into the long-term follow-up study (catch-up vaccination group). The primary efficacy endpoints were the incidence of external genital warts related to HPV6 or 11 and the incidence of external genital lesions related to HPV6, 11, 16, or 18 in all participants and the incidence of anal intraepithelial neoplasia (including anal warts and flat lesions) or anal cancer related to HPV6, 11, 16, or 18 in MSM only. The primary efficacy analysis was done in the per-protocol population for the early vaccination group, which included participants who received all three vaccine doses, were seronegative at day 1 and PCR-negative from day 1 through month 7 of the base study for the HPV type being analysed, had no protocol violations that could affect evaluation of vaccine efficacy, and had attended at least one visit during the long-term follow-up study. For the catch-up vaccination group, efficacy was assessed in the modified intention-to-treat population, which included participants who had received at least one vaccine dose, were seronegative and PCR-negative for HPV types analysed from day 1 of the base study to the final follow-up visit before receiving the quadrivalent HPV vaccine, and had at least one long-term follow-up visit. Safety was assessed in all randomised participants who received at least one vaccine dose. This study is registered with ClinicalTrials.gov, NCT00090285., Findings: Between Aug 10, 2010, and April 3, 2017, 1803 participants were enrolled in the long-term follow-up study, of whom 936 (827 heterosexual men and 109 MSM) were included in the early vaccination group and 867 (739 heterosexual men and 128 MSM) were included in the catch-up vaccination group. Participants in the early vaccination group were followed up for a median of 9·5 years (range 0·1-11·5) after receiving the third dose of the quadrivalent HPV vaccine, and participants in the catch-up vaccination group were followed up for a median of 4·7 years (0·0-6·6) after receiving the third dose. In early vaccine group participants during long-term follow-up compared with the placebo group in the base study, the incidence per 10 000 person-years of external genital warts related to HPV6 or 11 was 0·0 (95% CI 0·0-8·7) versus 137·3 (83·9-212·1), of external genital lesions related to HPV6, 11, 16, or 18 was 0·0 (0·0-7·7) versus 140·4 (89·0-210·7), and of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 in MSM only was 20·5 (0·5-114·4) versus 906·2 (553·5-1399·5). Compared with during the base study (ie, before quadrivalent HPV vaccine administration), during the long-term follow-up period, participants in the catch-up vaccination group had no new reported cases of external genital warts related to HPV6 or 11 (149·6 cases per 10 000 person-years [95% CI 101·6-212·3] vs 0 cases per 10 000 person-years [0·0-13·5]) or external genital lesions related to HPV6, 11, 16, or 18 (155·1 cases per 10 000 person-years [108·0-215·7] vs 0 cases per 10 000 person-years [0·0-10·2]), and a lower incidence of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 (886·0 cases per 10 000 person-years [583·9-1289·1] vs 101·3 cases per 10 000 person-years [32·9-236·3]). No vaccine-related serious adverse events were reported., Interpretation: The quadrivalent HPV vaccine provides durable protection against anogenital disease related to HPV6, 11, 16, and 18. The results support quadrivalent HPV vaccination in men, including catch-up vaccination., Funding: Merck Sharp & Dohme., Competing Interests: Declaration of interests SEG reports speaker honoraria from, and being an investigator for, Merck Sharp & Dohme (MSD) Corp, a subsidiary of Merck & Co (Kenilworth, NJ, USA); being an investigator for Inovio; receiving research support from Medtronic; and being a consultant for THD America. ARG reports receiving grants from MSD paid to her institution and being a member of the scientific advisory board for MSD. JMP reports grants and travel support from MSD during the conduct of the study; grants and personal fees from, and stock options in, Vir Biotechnology; stock options in Virion Therapeutics; and personal fees from Vaccitech, outside the submitted work. MEP reports funding from MSD relating to the conduct of the vaccine trials. EDM has been an investigator for HPV vaccine studies sponsored by MSD and is a member of the scientific advisory board for MSD. EB reports clinical investigator fees for this trial. HJ reports grants and non-financial support from Klinisches Studienzentrum für Infektiologie; personal fees from Hormosan Pharma, GlaxoSmithKline, Ifi-Medizin, and CIP Clinic; grants from Sanofi-Aventis Deutschland, CROMSOURCE, Centre Hospitalier Universitaire de Nantes, and the US Military HIV Research Program (MHRP); grants, personal fees, and non-financial support from, and board membership for, Gilead Sciences; personal fees and non-financial support from, and board membership for, ViiV Healthcare and AbbVie Deutschland; and personal fees and non-financial support from MSD and Janssen-Cilag, all during the conduct of the study. HJ also reports grants, personal fees, and non-financial support from, and board membership for, Gilead Sciences; grants from CROMSOURCE, Centre Hospitalier Universitaire de Nantes, and the US MHRP; personal fees and non-financial support from, and board membership for, ViiV Healthcare and Abbvie Deutschland; and personal fees from GlaxoSmithKline, MSD, Janssen-Cilag, Ifi-Medizin, and CIP Clinic, outside the submitted work. RK reports receiving consultation fees from MSD as a member of the pathology review panel. BMR reports consulting for MSD. MHS reports personal fees from MSD, Roche, Becton Dickinson, and Inovio Pharmaceuticals as a consultant, outside of the submitted work. OB, RD, TG, AL, HJZ, and AS are employees of MSD and might own stock or stock options in Merck. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. Published by Elsevier Ltd.. All rights reserved.)

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.)

Background: Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality., Methods: We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models., Findings: The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (p trend =0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (p trend <0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (p trend =0·0076); the prevalence plateaued thereafter (p trend =0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age., Interpretation: High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+., Funding: International Agency for Research on Cancer., Competing Interests: Declaration of interests ARG received travel fees from Merck & Co to participate in scientific advisory board meetings, and her institution has received grants for research from Merck & Co. SEH is funded by the US National Institutes of Health and the Bill & Melinda Gates Foundation outside the submitted work; and is a consultant for In Bios and a grant reviewer for US National Institutes of Health Study Section outside the submitted work. SEG received an investigator-initiated grant from Merck & Co, Inovio, and Medtronic outside the submitted work; consulting fees from THD America outside the submitted work; and payment as a speaker and financial support for attending meetings from Merck & Co outside the submitted work. MFSvdL received funds awarded to his institution from the AidsFonds charity and from Merck Sharpe & Dohme for participation on a data safety monitoring board or advisory board. KN is the recipient of a Miguel Servet research grant (CPII18/00033) from the Instituto de Salud Carlos III (Madrid, Spain) outside the submitted work. AGN received an investigator-initiated grant from Merck & Co in 2010–11 awarded to his institution at the time (Moffitt Cancer Center, Tampa, FL, USA) to assess the prevalence and incidence of anal HPV among men, allowing genotyping of samples (these data are included in the current Article); received travel fees from EUROGIN to present at their conferences; and received donated swabs and vials from COPAN. UW received grant support from the German Federal Ministry of Health for a study included in this report. EPFC is supported by an Australian National Health and Medical Research Council Emerging Leadership Investigator Grant (GNT1172873) outside the submitted work. YC received financial support from the Canadian Institutes of Health Research scholarship/studentship (CGS-D) outside the submitted work. YH received funding from the Natural Science Foundation of China International/Regional Research Collaboration Project (72061137007) and the Natural Science Foundation of China (81673232 and 82073574) outside the submitted work. GM received funding from US National Institutes of Health/National Cancer Institute outside the submitted work. APO received funds awarded to her institution from Aids Malignancy Consortium (2UM1CA121947–14) outside the submitted work; funds awarded to her institution from California-Mexico-Puerto Rico Partnership Center for Prevention of HPV-related Cancer in HIV-positive Populations (5U54CA242646–02) and from UPR/MDACC: Partnership for Excellence in Cancer Research (5U54-CA096297–17 and 5R21DE027226–02) outside the submitted work; and consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, and educational events from Merck & Co outside the submitted work. HZ received funding awarded to Sun Yat-sen University from the Natural Science Foundation of China Excellent Young Scientists Fund (82022064), the Natural Science Foundation of China International/Regional Research Collaboration Project (72061137001), and the Precision Targeted Intervention Studies among High Risk Groups for HIV Prevention in China, National Science and Technology Major Project of China (2018ZX10721102) outside the submitted work. All other authors declare no competing interests., (© 2021 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY-NC-ND 3.0 IGO license.)

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.)

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 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.)

Background: The progression rate and predictors of anal dysplastic lesions to squamous cell carcinoma of the anus remain unclear. Characterizing these parameters may help refine anal cancer screening guidelines., Objective: This study aimed to determine the rate of progression of high-grade anal dysplasia to invasive carcinoma in HIV-infected persons., Design: Using the Surveillance, Epidemiology, and End Results database linked to Medicare claims from 2000 to 2011, we identified HIV-infected subjects with incident anal intraepithelial neoplasia III. To estimate the rate of progression of anal intraepithelial neoplasia III to invasive cancer, we calculated the cumulative incidence of anal cancer in this cohort. We then fitted Poisson models to evaluate the potential risk factors for incident anal cancer., Settings: This is a population-based study., Patients: Included were 592 HIV-infected subjects with incident anal intraepithelial neoplasia III., Main Outcome Measures: The primary outcome measured was incident squamous cell carcinoma of the anus., Results: Study subjects were largely male (95%) with a median age of 45.7 years. Within the median follow-up period of 69 months, 33 subjects progressed to anal cancer. The incidence of anal cancer was 1.2% (95% CI, 0.7%-2.5%) and 5.7% (95% CI, 4.0%-8.1%) at 1 and 5 years, following a diagnosis of anal intraepithelial neoplasia III. Risk of progression did not differ by anal intraepithelial neoplasia III treatment status. On unadjusted analysis, black race (p = 0.02) and a history of anogenital condylomata (p = 0.03) were associated with an increased risk of anal cancer incidence, whereas prior anal cytology screening was associated with a decreased risk (p = 0.04)., Limitations: The identification of some incident cancer episodes used surrogate measures., Conclusions: In our population-based cohort of HIV-infected subjects with long-term follow-up, the risk of progression from anal intraepithelial neoplasia III to anal squamous cell carcinoma was higher than reported in other studies and was not associated with the receipt of anal intraepithelial neoplasia III treatment. See Video Abstract at http://links.lww.com/DCR/A933.

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.)

We examined the prevalence of infection with human papillomavirus (HPV) and HIV in a cohort of young gay, bisexual, and other men who have sex with men [sexual minority men (SMM)]. HPV vaccination uptake was assessed; HIV antibody testing was performed and genetic testing for oral and anal HPV infection was undertaken. We examined both HPV vaccination and infection in relation to key demographic and structural variables. Participants (n = 486) were on average 23 years old; 70% identified as a member of a racial/ethnic minority group, and 7% identified as transgender females. Only 18.1% of the participants indicated having received the full dosage of HPV vaccination and 45.1% were unvaccinated. Slightly over half the participants (58.6%) were infected with HPV, with 58.1% testing positive for anal infection and 8.8% for oral infection. HIV seropositivity was associated with infection to oral HPV [adjusted odds ratio (AOR) = 4.03] and vaccine-preventable HPV, whereas both neighborhood-level poverty (AOR = 1.68) and HIV infection (AOR = 31.13) were associated with anal infection to HPV (AOR = 1.68). Prevalence of HPV infection is high among unvaccinated young SMM, despite the availability and eligibility for vaccination. HPV infection adds further health burden to these populations and is particularly concerning for those who are HIV positive as HIV infection increases the risk of developing HPV-related cancers. These findings underscore a missed prevention opportunity for an at-risk and underserved population and suggest the need for active strategies to increase HPV vaccination uptake in young SMM before the onset of sexual behavior.

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: More than 90% of anal cancers are caused by human papillomavirus, and human papillomavirus strains 16 and 18 are the most oncogenic. Anal high-grade squamous intraepithelial lesions are cancer precursors. Treating these high-grade intraepithelial lesions likely reduces the risk of cancer, but cytology is an imperfect screening test., Objective: The purpose of this study was to determine whether human papillomavirus 16 and/or 18 testing better predicts the presence of high-grade squamous intraepithelial lesions., Design: In this retrospective study, 894 consecutive patients underwent anal dysplasia screening with digital anorectal examination, anal cytology, high-risk human papillomavirus testing, and high-resolution anoscopy with biopsy. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of each test and for a novel screening protocol. The absolute and relative risk of high-grade squamous intraepithelial lesions for all of the cytology/human papillomavirus combinations were also calculated., Settings: The study was conducted at a single practice specializing in anal dysplasia., Patients: Ninety-two percent of participants were men who have sex with men. Forty-four percent were HIV-positive individuals who were well controlled on antiretroviral therapy. The median age was 50 years., Main Outcome Measures: The presence of high-grade squamous intraepithelial lesions as a function of human papillomavirus and the cytology results were measured., Results: High-risk human papillomavirus testing alone demonstrated better sensitivity (96% vs 89%; p = 0.03) and negative predictive value (99% vs 96%; p = 0.008) over cytology. Human papillomavirus 16/18 testing increased specificity (48% to 71%; p < 0.0001) and positive predictive value (24% to 37%; p = 0.003) over testing for all of the high-risk strains. For each cytology category, high-grade squamous intraepithelial lesions were more prevalent when human papillomavirus 16/18 was detected. Benign cytology with 16/18 had a 31-fold increased risk of high-grade squamous intraepithelial lesions., Limitations: This study was conducted in a single private practice specializing in anal dysplasia screening with a mostly male population, and results might not be generalizable., Conclusions: Testing of high-risk human papillomavirus strains 16/18 improves specificity and positive predictive value over cytology for anal dysplasia screening. Patients testing positive for strains 16/18 are at a high risk for high-grade squamous intraepithelial lesions and should undergo high-resolution anoscopy regardless of the cytology result. See Video Abstract at http://links.lww.com/DCR/A654.

Background: HIV-positive individuals have high incidence of anal high-grade squamous intraepithelial lesions (HSIL) at the squamocolumnar junction (SCJ), which can progress to cancer. Focal radiofrequency ablation (RFA) treats HSIL, but metachronous recurrence remains high and may be improved with circumferential treatment., Setting: The study was performed at a single center., Methods: This was a prospective trial of circumferential anal RFA using Barrx 60 RFA focal catheters in participants with ≥1 anal SCJ HSIL. The entire SCJ was ablated by RFA. Adverse events (AEs), symptoms, including pain, and quality of life were assessed. High-resolution anoscopy assessed recurrences at 3, 6, 9, and 12 months. Lesion site biopsies occurred at month 12. Recurrences were retreated with focal RFA., Results: Ten male participants (9 HIV+), with a median 2 HSILs (range 2-8) each, enrolled. Median T-cell count and viral load were 730 cells/mcL and 38 copies/mL. Median duration of RFA treatment was 6.5 (5-13) minutes. Lesion persistence occurred in 4 participants (3 at 3 months, 1 at 6 months). Recurrence at a new site occurred in 1 participant at 3 months. No lesion persisted after retreatment. All participants were HSIL free and completely healed by 12 months. Two device-related mild AEs occurred in 1 participant each (thrombosed external hemorrhoid and soft anal scar; both resolved). No serious AEs occurred., Conclusion: Circumferential anal SCJ RFA produced total HSIL eradication with no more than 2 treatments. Circumferential RFA seems to be well tolerated with minimal pain and no serious AEs in HIV+ participants. CLINICALTRIALS.GOV:: NCT02189161.

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.)

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.)

Background: Anal canal high-grade squamous intraepithelial lesion (HSIL) is the precursor to anal cancer. Immunocompromised patients are at increased risk and disease is usually within 3 cm from the anal verge. High-resolution anoscopy (HRA) with an 8-cm anoscope is used to identify and guide cautery treatment of HSIL., Purpose: We report three patients with a long-term history of ulcerative colitis (UC) treated with systemic immunomodulators who developed proximally located rectal HSIL., Results/outcomes: Two patients were HIV-negative women, 63 and 48 years old, and the third was a 51-year-old HIV-positive man with underlying UC for 10, 16, and 3 years, respectively. They each presented with a HPV-positive HSIL visibly extending above the limits of the anoscope used for HRA. None developed cancer. All had episodes of active UC. It is unclear what causative role systemic immunomodulators play in predisposing UC patients to proximal HSIL. HSIL probably developed on a tongue of HPV-infected squamous epithelium growing proximally over the inflamed rectum. Islands developed when areas of squamous epithelium degenerated, creating skip areas., Discussion: This study highlights the potential for HSIL to extend into the rectum either as a contiguous patch or isolated islands and the need for heightened surveillance in patients with extensive anal canal HSIL treated with immunodulator therapy. HSIL identified at the limit of the anoscope should be investigated further with colonoscopy, and argon plasma coagulation (APC) ablation can serve as an effective treatment option. Patients are at risk for stricture, but it is unclear what role the UC or the ablation played in stricture formation.

Purpose: Radiofrequency ablation (RFA) effectively treats esophageal high-grade dysplasia, but its efficacy in treating anal canal high-grade squamous intraepithelial lesions (HSILs) is unsubstantiated. This prospective study assessed the safety and efficacy of applying hemi-circumferential RFA to anal canal HSIL., Methods: Twenty-one HIV-negative participants with HSIL occupying ≤ half the anal canal circumference were treated with hemi-circumferential anal canal RFA. Participants were assessed every 3 months for 12 months with high-resolution anoscopy; recurrence in the treatment zone was re-treated with focal RFA., Results: Twenty-one participants with a mean of 1.7 lesions (range 1-4) enrolled and completed the trial. Six (29 %) participants had recurrent HSIL within the treated hemi-circumference within 1 year. Four participants (19 %) had persistence of an index lesion at 3 months. One (2.9 %) index HSIL persisted again at 12 months. No participants had more than two RFA treatments. KM curve-predicted HSIL-free survival within the treatment zone at 1 year was 76 % (95 % CI 52-89 %). Comparing the first 7 and last 14 participants, the predicted 1-year HSIL-free survivals are 43 % (95 % CI 10-73 %) and 93 % (95 % CI 59-99 %), respectively (p = 0.008), suggesting a learning curve with the treating physician. Multivariable analysis showed decreased recurrence in the last 14 participants (HR 0.02; 95 % CI 0.001-0.63) while increasing BMI increased recurrence (HR 1.43, 95 % CI 1.01-2.01). No participants had device or procedure-related serious adverse events, anal stricture, or heavy bleeding., Conclusions: Hemi-circumferential RFA yielded a high rate of anal HSIL eradication in HIV-negative patients at 1 year with minimal adverse events. Lesion persistence was probably related to incomplete initial ablation.

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.

Background: Perianal high-grade dysplasia (Bowen disease) is traditionally treated with mapping and wide excision with possible grafting rather than local ablation., Objective: The aim of this study is to examine the results of high-grade perianal dysplasia ablation., Data Sources: Data for this study were derived from a retrospective chart review at a surgical practice screening and treating patients for high-grade dysplasia between July 1998 and June 2013., Study Selection: The patients included were men who have sex with men and are undergoing perianal dysplasia ablation., Intervention: Ablation of perianal dysplasia with electrocautery, laser, or infrared coagulation was performed., Main Outcome Measures: The primary outcomes measured were the recurrence of perianal dysplasia postablation and factors affecting recurrence., Results: Seventy HIV-positive and 11 HIV-negative patients enrolled; the median ages were 44.7 and 42.8 years. Median follow-up times for HIV-positive and HIV-negative patients were 4.62 and 3.53 years, and the median numbers of treatments were 4 and 1, p = 0.004. The median number of lesions treated was 1 for both groups. Only 1 HIV-negative patient had a recurrence 8 months after treatment. For HIV-positive patients, the Kaplan-Meier probability of recurrence at 1, 3, and 5 years was 38% (95% CI 26-50), 59% (95% CI 47-72), and 68% (95% CI 55-81) after the first ablation with no difference for subsequent treatments. HIV-positive patients had a relative risk of perianal high-grade squamous intraepithelial lesions of 3.72 (95% CI 2.10-6.60) compared with HIV-negative patients (p ≤ 0.0001). In multivariate analysis, only each increase in intra-anal high-grade squamous intraepithelial lesions significantly increased recurrence (HR 1.13, 95% CI 1.00-1.28, p = 0.002). Only 3 patients with perianal high-grade squamous intraepithelial lesions did not have canal dysplasia. Perianal cancer developed in 3 after being lost to follow-up., Limitations: This is a retrospective analysis of 1 experienced surgeon's results. No precise way exists to accurately determine the size of the disease., Conclusions: Perianal dysplasia can be successfully ablated, but recurrence remains high. Almost all patients have anal canal dysplasia. HIV-positive patients are at the greatest risk for disease and recurrence. An increased number of high-grade canal lesions increases recurrence.

Background: Men who have sex with men have increased prevalence of both human papillomavirus and anogenital condyloma., Objective: Risk factors for multiple treatment and recurrence of anal condyloma were examined., Design: This is a retrospective study of HIV-negative men who have sex with men who were treated for anal condyloma., Settings: This study was conducted in a private surgical practice., Patients: The patients were HIV-negative men who have sex with men, aged 18 years or older., Intervention(s): Ablation with electrocautery or CO2 laser was performed, as well as excision and topical imiquimod condyloma treatment adjuvant., Main Outcome Measures: Primary clearance, defined as 4 months of condyloma-free survival posttreatment, and recurrence, defined as any anal condyloma diagnosis after primary clearance., Results: Of 231 participants, 207 achieved primary clearance (median age, 32.0 years) and were followed (median, 18.2 months) after primary treatment. Most had intra-anal and perianal condyloma (56%), were treated with electrocautery ablation (79.2%), and required 1 treatment (range, 1-6) for clearance. There were 57 recurrences (median, 12 months). One-third each had minimal, moderate, or extensive disease. Forty-six percent of patients received imiquimod posttreatment adjuvant. High-grade dysplasia was found in 31% at presentation and 43% during follow-up. Factors associated with requiring multiple treatments for clearance were participants having moderate disease (adjusted odds ratio, 6.0 (1.7-21.4)) and receiving imiquimod adjuvant (adjusted odds ratio, 4.7 (2.0-10.6)). No single factor predicted recurrence, but those with moderate disease experienced recurrences significantly sooner (median, 25 months of follow-up)., Limitations: This was a retrospective chart review, it was limited to a single practice, and it excluded those who did not achieve primary clearance., Conclusions: Most men who have sex with men have intra-anal and perianal condyloma and concomitant high-grade dysplasia is common. Most achieved clearance with 1 treatment. Having both intra-anal and perianal condyloma, increased severity of disease, and imiquimod adjuvant were significant predictors of requiring multiple treatments for clearance. No identified risk factors proved a significant predictor of recurrence.

Background: The quadrivalent human papillomavirus vaccine (qHPV) is FDA-approved for use in males 9 to 26 years old to prevent anogenital condyloma. The objective of this study is to determine if qHPV is effective at preventing anal condyloma among men who have sex with men (MSM) aged 26 years and older., Methods: This post-hoc analysis of a nonconcurrent cohort study evaluated 210 patients without history of anal condyloma and 103 patients with previously-treated anal condyloma recurrence-free for at least 12 months prior to vaccination/time zero. We determined the rate of anal condyloma development in vaccinated versus unvaccinated patients., Results: 313 patients with mean age 42 years were followed for median 981 days. During 773.6 person-years follow-up, condyloma developed in 10 (8.6%) vaccinated patients (incidence of 3.7 per 100 person-years) and 37 (18.8%) unvaccinated patients (incidence 7.3 per 100 person-years; p = 0.05). Multivariable hazards ratio showed that qHPV was associated with decreased risk of anal condyloma development (HR 0.45; 95% CI 0.22-0.92; p = 0.03). History of anal condyloma was associated with increased risk of anal condyloma development (HR 2.28; 95% CI 1.28-4.05; p = 0.005), as was infection with oncogenic HPV (HR 3.87; 95% CI 1.66-9.03; p = 0.002)., Conclusions: Among MSM 26 years of age and older with and without history of anal condyloma, qHPV reduces the risk of anal condyloma development. A randomized controlled trial is needed to confirm these findings in this age group.

Background: Colorectal surgeons are ideal referral sources to screen for and treat high-grade anal dysplasia (high-grade squamous intraepithelial lesion [HSIL]) and anal cancer. Anal cytology and high-resolution anoscopy (HRA) using acetic acid and magnification are optimal methods for screening. We endeavored to determine US colorectal surgeons' attitudes and practices regarding HSIL screening., Methods: An Internet-based survey with questions related to clinician demographics and attitudes and practices regarding anal dysplasia was sent to US members of the American Society of Colon and Rectal Surgeons., Results: Of 1655 requests, 290 (18%) eligible participants responded. Most were white (83%), male (76%), board-certified colorectal surgeons (89%), and graduating medical school after 1990 (54%), almost all treated patients at risk for anal cancer and had read research on HSIL. Approximately one-third of respondents had performed anal cytology, and one-third had performed HRA. When evaluating patients for HSIL in surgery, only 31% use acetic acid with magnification. Of 99 participants who perform HRA, 46% were formally trained, 83% primarily do HRA primarily in the operating room, and 82% use acetic acid with magnification. Knowledge of HSIL risk factors was not associated with screening. Women, more recent graduates, and surgeons with higher percentages of HIV-infected patients were more likely to screen. Screening barriers included no training (52%), not a priority (23%), lack of evidence (21%), and cost (8%)., Conclusions: American Society of Colon and Rectal Surgeons members responding to the survey by and large do not screen for anal dysplasia. Those that do are often not formally trained and use inadequate technique.

Background: High-grade dysplasia is the anal carcinoma precursor. Clinicians ablate high-grade dysplasia with laser, electrocautery, and infrared coagulation to prevent cancer., Objective: The aim of this study was to determine the long-term effectiveness of high-grade dysplasia ablation and the incidence of cancer., Design: This study is a retrospective chart review of patients who were treated for high-grade dysplasia from February 1998 until May 2012., Setting: This study was conducted in a surgical practice screening patients for anal cancer and high-grade dysplasia., Patients: The patients identified were HIV-positive and -negative men who have sex with men., Intervention: The ablation of high-grade dysplasia was performed., Main Outcome Measures: The primary outcomes measured were the probability of high-grade dysplasia recurrence postablation and the incidence of cancer., Results: Four hundred fifty-six HIV-positive men who have sex with men (mean age, 45 ± 9 years) and 271 HIV-negative men who have sex with men (mean age, 41 ± 11 years) followed for a median of 2.2 (range, 0.2-13) years underwent high-grade dysplasia ablation by laser, infrared coagulation, and/or electrocautery. Median time to recurrence was 6.8 and 6.9 months for HIV-positive and -negative patients. Kaplan-Meier curves predict a rate of recurrence 1 year after the first ablation for HIV-positive and -negative patients of 53% (95% CI, 49%-58%) and 49% (95% CI, 43%-55%). At 2 and 3 years, the rate of recurrence was 68% (95% CI, 63%-73%) and 77% (95% CI, 7%2-82%) for HIV-positive patients and 57% (95% CI, 51%-64%) and 66% (95% CI, 59%-73%) for HIV-negative patients. The median number of recurrent lesions was ≤2 for HIV-positive patients and ≤1 for HIV-negative patients. Recurrence increased with HIV infection (HR, 1.3; 95% CI, 1.1-1.6) and each additional lesion treated (HR 1.6, 95% CI, 1.1-1.2). Five HIV-positive men who have sex with men developed cancer. The Kaplan-Meier probability of cancer 3 years postablation was 1.97% (95% CI, 0.73%-5.2%)., Limitations: This is a retrospective study by 1 surgeon who has extensive experience treating anal dysplasia. There was no pathology review, and the type of recurrence cannot be definitively determined because the location could be inaccurate., Conclusions: Patients undergoing ablation of intra-anal high-grade dysplasia have high recurrence, but the probability of developing anal cancer is low. HIV infection and increased number of high-grade dysplasias increases the risk of recurrence.

Objective: Random biopsy (RB) of normal appearing cervix during colposcopy increases high-grade dysplasia (HSIL) diagnosis but has not been studied in high-resolution anoscopy (HRA), that is, colposcopy transferred to the anal canal. We investigated the utility of RB during HRA., Design: At HRA, the anal canal was divided into 4 quadrants. Areas suspicious for HSIL had standard biopsy (SB); random biopsies were taken from quadrants without apparent HSIL. Inclusion required ≥1 RB. Two providers performed all procedures (S.E.G., >10 years experience; M.M.G. 3 years experience)., Results: Overall, 391 participants enrolled (mean age, 44.7 years); most were male (87.2%), non-Hispanic (69.8%), white (62.7%), and HIV positive (72.9%). Of 1761 biopsies, 883 were RBs (mean, 2.26/participant). HSIL was identified in 252 lesions, and in 132 participants (33.8%). Thirty-two HSILs (12.7%) and 13 participants (9.8%) were diagnosed by RB. RB increased total HSILs identified per participant (mean, 0.65 vs. 0.56; P < 0.001) and participants with HSIL (P < 0.001). Histologically, HSIL diagnoses via SB were no more dysplastic than random biopsies (relative risk, 0.82; range, 0.37-1.8). In multivariable analysis, factors affecting adjusted relative risk (ARR) of HSIL with any biopsy were provider [S.E.G vs. M.M.G.; ARR, 5.9; 95% confidence interval (CI), 1.3 to 25.8] and oncogenic human papillomaviral infection (ARR, 24.3; 95% CI, 2.8 to 213.3). Risk of HSIL on RB alone in multivariate analysis was associated with HSIL via SB (ARR, 3.4; 95% CI, 1.6 to 7.1 or ARR, 1.4; 95% CI, 1.1 to 1.9 per standard HSIL). Provider, HIV status, detectable viral load, age, or prior screening for or treatment of HSIL did not affect the utility of RB., Conclusions: Addition of RB to HRA significantly increased both the number of HSILs and participants with HSIL identified.

Objective: The incidence of anal human papillomavirus (HPV) infection and of HPV-related disease in men who have sex with men continues to rise. Screening procedures can be uncomfortable and may lead to decreased patient compliance. We endeavored to determine the tolerability of screening procedures for anal HPV disease., Materials and Methods: This was a 2-visit screening study. On visit 1 (V1), cells for cytology (using a swab) and HPV testing (randomized to a brush or swab) were collected, followed by digital rectal examination and standard anoscopy. At visit 2 (V2), patients had repeated HPV sampling (brush or swab) and high-resolution anoscopy with biopsy where indicated. Patients reported discomfort of procedures (0-5) and complications., Results: Visit 1 standard anoscopy caused the most discomfort (mean = 1.90). Visit 2 biopsy caused the least discomfort (mean = 1.04). The mean discomfort difference between V1 HPV sampling with swab (1.56) and brush (1.86) was significant (p = .03) but not at V2. The mean difference between V2 HPV brush (1.63) and V1 brush (1.86) discomfort was significant (p = .02), but there was no significant difference for V1 and V2 swab. There was no discomfort difference between standard anoscopy and high-resolution anoscopy (p = .14). All patients who reported at V1 that the discomfort would prevent them from having procedure again returned for V2. There was no significant difference in bleeding or pain after V1 for brush or swab., Conclusions: Screening procedures for anal HPV-related disease were well tolerated, and no single procedure or HPV sampling device reduced patient compliance.

A small number of HPV types are related to a majority of HPV-related neoplastic lesions in humans. High-risk types such as HPV 16 and 18 are most often implicated, although other oncogenic and non-oncogenic HPV types can cause disease in men. The efficacy of the quadrivalent HPV vaccine (qHPV) against external genital lesions and intra-anal disease related to HPV in men has been demonstrated. This report examines the vaccine's efficacy against disease due to 10 additional non-vaccine HPV types, as well as efficacy regardless of HPV detection. The data presented suggest that vaccinating males against HPV 6, 11, 16 and 18 protects them against most vaccine HPV-type related anogenital disease. However, significant efficacy against disease due to non-vaccine HPV types was not seen. In addition, the data do not provide any evidence that vaccination with qHPV vaccine will increase the likelihood of disease caused by non-vaccine types in the short term., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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.

Hybrid Capture 2 (HC2) Human Papillomavirus (HPV) DNA Test® is FDA approved and is a proven aid in detecting HPV infections of the cervix and as an aid in diagnosing, with cytology, cervical disease. A prospective feasibility study was conducted to determine if HC2 testing has utility when screening for high-grade anal dysplasia (AIN2+). We enrolled 298 patients (45% HIV+) who had AIN2+ screening with cytology, histology and HC2 testing for two specimens: a swab into liquid-based cytology medium and either a swab or a brush collection in specimen transport medium (STM). High-resolution anoscopy was performed on all patients with biopsy of AIN2+ suspicious lesions. Cytology was benign (42%), atypical squamous cells of undetermined significance (30%), low-grade squamous intraepithelial lesion (18%), high-grade squamous intraepithelial lesion (1%), ASCUS possibly high-grade dysplasia (1.7%) and nondiagnostic (7%) and 36% had AIN2+ histology. Sensitivity and specificity for predicting AIN2+ histology for any abnormal cytology were 77 and 52%, whereas HC2 sensitivity and specificity were 91 and 40% (p = 0.005 for sensitivity), respectively. There was no significant difference in HC2 sensitivity or specificity between brush and swab or STM and residual cells from cytology. AIN2+ was found in 20% of patients with benign cytology. Only nine AIN2+ specimens were HC2-. This prospective study indicates that HC2 may be useful when screening for anal dysplasia; however, a larger study is recommended., (Copyright © 2012 UICC.)

The hc2 human papillomavirus DNA test (HC2) is effective when screening women for cervical dysplasia, and it might be effective in the screening for anal dysplasia. Differences between the anal and the cervical canals could affect the test performance. This prospective study (n=292) measured the HC2 signal and in agreement with a histologic endpoint of high-grade dysplasia for anal specimens collected in various ways. Sensitivities were 91%, 85%, and 62% for specimens collected in a sample transport medium and a liquid-based cytology medium processed by Gyn or Non-Gyn protocol, respectively. HC2 sensitivity and specificity to predict high-grade anal dysplasia were similar for brush or swab specimen collections, but HC2 signal was 6 times higher with the brush. Specificity and sensitivity were similar whether the sample was collected first or after a cytology sample for brush or swab, but swab specimens at the second collection had an HC2 signal (mean) 48% lower than that of the first collection, and the swab cellularity was lower. The presence of maximum stool decreased the HC2 signal in anal swab specimens. Consensus polymerase chain reaction (PCR) confirmed that the 13 human papillomavirus probe types in HC2 were optimal for performance. HC2 could potentially be further investigated for use in screening anal dysplasia. A larger prospective study is indicated.