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Objectives Anal squamous cell carcinoma (ASCC) has a higher incidence described in certain groups, namely, in women with vulvar high-grade squamous intraepithelial lesions (vHSILs) and/or human papillomavirus squamous cell carcinoma (VSCC). This review describes terminology, vHSIL, and VSCC in their association with ASCC and the published recommendations for early detection of this cancer in these women. Materials and methods A narrative review was conducted by the authors on vHSIL and VSCC as risk factors for ASCC. Results The ASCC and VSCC incidence are increasing. Women with vHSIL and/or VSCC can present with ASCC at diagnosis, being one of the highest-risk groups. Suspicious symptoms include rectal bleeding, pain, and a sensation of an anal mass. Digital anorectal examination can help detect early ASCC. Sensitivity of anal cytology in women with vHSIL and VSCC seems low, with the exception of immunosuppressed women with genital neoplasia (cervix, vagina, and vulva). There are still insufficient data on high-resolution anoscopy in women with vHSIL and/or VSCC as a screening method. Conclusions Clinicians need be aware that women with vHSIL and VSCC comprise one of the highest-risk groups for ASCC. Inquiring suggestive symptoms of ASCC and a digital anorectal examination can help in the early detection of this type of cancer.

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

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

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.

Objectives Anal cytology is a modality for anal cancer screening in high-risk women. In this retrospective study, we review risk factors associated with abnormal anal cytology and unsatisfactory anal cytology rates, and correlate findings of cytology with histological results. Methods A retrospective cohort study of anal cytology screening in women at Mayo Clinic in Rochester, Minnesota from 2002 to 2018 was conducted. Results Three hundred fifty-seven women had a total of 592 anal cytologies performed. Three hundred seventeen women had screening anal cytology, whereas 40 women had anal cytology for surveillance given a history of anal intraepithelial neoplasia (AIN) or anal cancer. An unsatisfactory anal cytology result was found in 14.7%. Risk factors, type of follow-up, and correlation with histologic specimens were also reviewed. Histologic finding of AIN 2/3 correlated with abnormal anal cytology 84% of the time in this cohort. Conclusions High-risk women should be screened on a periodic basis for anal cancer. Anal cytology is one possible modality that can be used. Further insight into AIN progression, regression, recurrence, and outcome after treatment will help direct future screening recommendations.

OBJECTIVE The aim of the study was to evaluate the validity of anal cytology against high-resolution anoscopy in the detection of anal high-grade squamous intraepithelial lesions (HSILs) among women in a clinical setting in Puerto Rico, alone and in combination with high-risk human papillomavirus (HR-HPV) typing. MATERIALS AND METHODS A cross-sectional study was done among 128 eligible women who attended the Anal Neoplasia Clinic of the University of Puerto Rico Comprehensive Center between 2014 and 2019. Kappa (κ) coefficient, sensitivity, specificity, positive predictive value, and negative predictive value were calculated using high-resolution anoscopy with biopsy as the criterion standard test. Poisson regression was used to estimate the adjusted prevalence ratio of anal HR-HPV infection. RESULTS Overall, 71.1% of women were HIV infected and 78.9% had anal HR-HPV infection. Squamous intraepithelial lesions were detected with anal cytology and histology in 70.3% and 81.3% of women, respectively. The κ statistic between the tests (cytology and histology) was 0.32 (p < .05). Measured against the results from histology, the sensitivity of anal cytology alone to detect HSIL was 85.4% (95% CI = 72.2%-93.9%), whereas specificity was 38.8% (95% CI = 28.1%-50.3%). Although the sensitivity of the 2 tests combined (anal cytology and HR-HPV typing) to detect histologically confirmed HSIL increased (100.0%, 95% CI = 92.6%-100.0%), the specificity decreased (16.3%, 95% CI = 9.0%-26.2%). Meanwhile, women with HSIL had a higher prevalence of anal HR-HPV infection than those with no SIL/LSIL (prevalence ratio = 6.23, 95% CI = 1.50-25.83). CONCLUSIONS Anal cytology in combination with HR-HPV typing for the screening of anal intraepithelial neoplasia improved the detection of HSIL in women.

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

ObjectiveThe objective of this study was to determine the performance characteristics of the Tush brush (TB) compared with a saline moistened Dacron swab (DS) as anal cytology sampling devices.Materials and methodsTB and DS anal cytology tests were randomly collected from 146 patients presenting for anal cytology. High-resolution anoscopy and biopsies were obtained as indicated. Sensitivity and specificity as well as rates of satisfactory specimens were determined for each method using the areas under the receiver operating characteristic curve (AUCROC) and McNemar's test, respectively. Perceived discomfort of each device was determined using a visual analog scale and compared using a paired t test.ResultsThe adjudicated AUCROC, sensitivity, and specificity were greater, but not significantly different, for the brush (0.63, 85.5, and 40.0, respectively) compared with the swab (0.50, 79.6, and 33.3, respectively) when the anal biopsy results were considered the criterion standard. In the 1 subject diagnosed with anal cancer, the swab cytology result was normal, but the brush result was abnormal. Specimen adequacy was 95.2% for the brush and 93.2% for the swab. Mean discomfort (visual analog scale) scores were swab 28.5 mm versus brush 35.6 mm (p = .0003) with both scores within the minimal to moderate discomfort range.ConclusionsAnal cytology AUCROC, sensitivity, and specificity in detecting anal neoplasia were greater using the TB when compared with the DS. A novel anal cytology sampling device designed specifically to increase the detection of anal neoplasia would be clinically beneficial.

OBJECTIVE: Anal cancer screening has been recommended for women with lower genital tract neoplasia (LGTN), lupus, Crohn’s disease, human immunodeficiency virus (HIV) and/or organ transplantation recipients. This study described and compared knowledge, attitudes, and experiences related to anal cancer and anal cancer screening between women at high-risk for anal cancer and their counterparts. METHODS: This is a Cross-sectional study within colposcopy and gynecology oncology clinics in Puerto Rico; 283 women aged ≥21 years or older and with prior diagnosis of gynecological neoplasia completed an interviewer-administered questionnaire. Women were categorized according to their medical history as being high-risk or non-high-risk for anal cancer. The high-risk group included women with history of lower genital tract neoplasia, lupus, Crohn’s disease, HIV and/or organ transplantation. RESULTS: Overall, 40.7% of the study population were at high-risk of developing anal cancer. History of anal cancer screening was low among high-risk and non-high-risk women (11.5 vs. 5.6%, p>0.05). Less than 1% of all women reported to have had a high-resolution anoscopy. Most women (87.6%) had little knowledge about anal Pap: test but were willing to have one if their doctors recommended it (96.5%). No major differences in knowledge, attitudes or screening history were observed between high-risk and non-high-risk women. CONCLUSION: Although experts do not recommend routine anal cancer screening for the general population, they do recommend it for women within certain high-risk groups. Study findings highlight the importance of increasing education and awareness of anal cancer among high-risk patients and physicians, to promote better preventive methods, achieve early detection and improve disease outcomes.

OBJECTIVE The purpose of this study was to assess knowledge of human papillomavirus (HPV) as a cause of anal cancer among at-risk gay, bisexual, and other men who have sex with men (GBM). MATERIALS AND METHODS Secondary analysis was conducted of cross-sectional data from 3 cycles of the Health Information National Trends Survey (2017, 2018, 2019). Results were reported for the subset of adults who identified as GBM (N = 212). Knowledge that HPV can cause anal cancer was the main outcome. Differences in knowledge were evaluated (using χ2 and multiple logistic regression) by demographic, health information factors, and access to care. RESULTS Sixty-eight percent of GBM were aware of HPV. Knowledge that HPV causes anal cancer was low (

Objective The aim of the study was to describe the clinicopathologic features of vulvovaginal or anal high-grade squamous intraepithelial lesion (HSIL) comorbid with lichen sclerosus and/or lichen planus (LS/LP). Methods The local pathology database identified 37 consecutive cases from 2007 to 2019 of vulvar, vaginal, or anal HSIL among women who had a histopathologic diagnosis of vulvar LS/LP. Cases had p16 and p53 immunoperoxidase stains. Clinical data included age, relative location of HSIL and LS/LP, immune-modifying conditions, tobacco use, treatment type, and follow-up. Histopathologic data included HSIL morphology categorized as warty-basaloid or keratinizing, p16 and p53 patterns within HSIL, and features of LS/LP. Results The mean age was 69 years with a median follow-up up 42 months. Lichen sclerosus, alone or in combination with LP, was the comorbid dermatosis in 89%. Lichen sclerosus/lichen planus was overlapping or adjacent to HSIL in two-thirds of cases and located separately in the remainder. Rates of tobacco use and immunologic dysfunction were each 40%. In cases of co-located LS and HSIL, sclerosis was absent under the neoplasia in 57%. Twenty-four percent of HSIL cases showed keratinizing morphology; block-positive p16 and suprabasilar-dominant p53 helped distinguish HSIL from human papillomavirus-independent neoplasia. Conclusions Histopathologic identification of comorbid HSIL and LS/LP may be challenging because of keratinizing morphology and loss of diagnostic features of LS. Clinicopathologic correlation and use of p16 and p53 are essential to achieve an accurate diagnosis and enact disease-specific management plans.

Objective Anal high-grade squamous intraepithelial lesion (HSIL) may precede invasive cancer and can be detected clinically or during high-resolution anoscopy (HRA). The aims of this study were to compare the characteristics of HSIL discovered by HRA or in a surgical specimen without clinically visible lesion when diagnosed versus macroscopic HSIL when first diagnosed and then to compare their progression to invasive cancer. Patients and methods Clinical records of all patients with at least one HSIL lesion confirmed by histology and evaluated by HRA in a single center between September 1, 2009, and April 30, 2017, were retrospectively reviewed. The center's histological anal cancer data base was questioned in December 2017 to identify all cases. Results During a median (interquartile range) follow-up of 19.1 (5.6-40.2) months, 12 (2.9%) anal cancers were diagnosed in patients with a diagnosis of HSIL. Period of time between the first diagnosis of anal lesion and the cancer was 28.8 months (interquartile range = 15.4-65.6), and 11 (92%) of 12 were diagnosed as superficially invasive squamous cell carcinoma or T1N0M0. The rate of progression to anal cancer differed significantly between patients with macroscopic HSIL at diagnosis (5.4%) and patients with microscopic HSIL diagnosed during HRA (0.9%) (p = .01). Conclusions Patients with macroscopic histologically proven HSIL at first diagnosis of anal intraepithelial lesion have a significantly higher risk of anal cancer compared with patients with microscopic lesions diagnosed during HRA, but the duration between the first diagnosis of HSIL and cancer does not differ between the 2 groups.

The aim of the study was to estimate the magnitude of the association between HPV-related gynecological neoplasms and secondary anal cancer among women in Puerto Rico (PR).We identified 9,489 women who had been diagnosed with a primary cervical, vaginal, or vulvar tumor during 1987-2013. To describe the trends of invasive cervical, vulvar, vaginal, and anal cancer, the age-adjusted incidence rates were estimated using the direct method (2000 US as Standard Population). Standardized incidence ratios (observed/expected) were computed using the indirect method; expected cases were calculated using 2 methods based on age-specific rates of anal cancer in PR. The ratio of standardized incidence ratios of anal cancer was estimated using the Poisson regression model to estimate the magnitude of the association between HPV-gynecologic neoplasms and secondary anal cancer.A significant increase in the incidence trend for anal cancer was observed from 1987 to 2013 (annual percent change = 1.1, p.05), whereas from 2004 to 2013, an increase was observed for cervical cancer incidence (annual percent change = 3.3, p.05). The risk of secondary anal cancer among women with HPV-related gynecological cancers was approximately 3 times this risk among women with non-HPV-related gynecological cancers (relative risk = 3.27, 95% CI = 1.37 to 7.79).Anal cancer is increasing among women in PR. Women with gynecological HPV-related tumors are at higher risk of secondary anal cancer as compared with women from the general population and with those with non-HPV-related gynecological cancers. Appropriate anal cancer screening guidelines for high-risk populations are needed, including women with HPV-related gynecological malignancies and potentially other cancer survivors.

Objective The aim of the study was to assess risk factors for anal human papillomavirus (HPV) infection and anal dysplasia among a cohort of transgender women (TGW). Methods A retrospective chart review was conducted based on electronic medical records of TGW patients seen in the University of Miami Health System between 2010 and 2016. Outcome measures included risk factors of anal dysplasia, including HIV infection, receptive anal intercourse, and smoking history. Descriptive statistical analysis and χ testing were used. Results Sixty-nine TGW patients' charts were reviewed. Patients' ages ranged from 18 to 72 (mean = 38 [15]). Twenty-two (30%) were older than 50 years; 10 (15%) were black/African descent; 20 (29%) reported a smoking history; 6 (9%) were HIV positive, and 28 (72%) among those with known partner preference (n = 39) reported male partners. Male partner preference was significantly associated with being black/African descent (p = .009) and being single (p = .048). Older age was significantly associated with HIV-positive status (p = .023). The average number of risk factors per person was 2.10 (0.97). Sixty-one years or older had the highest average number of risk factors (2.90 [0.88]). Conclusions Because rates of HIV, dangerous sexual behaviors, and other risk factors for anal dysplasia continue to persist among TGW, this study reinforces the need to increase the focus on anal health in the care of TGW and the need for further research to guide patient care and anal dysplasia screening strategies among those individuals.

OBJECTIVES This study aimed to evaluate the incidence of anal dysplasia in women at high risk of developing those lesions and to assess the relationships between positive anal cytology and different risk factors. MATERIALS AND METHODS We performed an observational cross-sectional study involving a patient survey and chart review. The study was conducted at the cervical pathology unit at the Hospital Universitario 12 de Octubre, Madrid, Spain, from 2011 to 2015. Patients were 215 women aged 18 to 65 years old with risk factors for anal dysplasia, for whom anal evaluation was indicated. Anal cytology was performed in all patients. High-resolution anoscopy and anal biopsy were used to investigate abnormalities. All patients completed a survey regarding sexual practices. The patients' demographic and clinical data were collected by using a retrospective chart review. The main outcome measure was the incidence of anal dysplasia in this population. RESULTS Of the 215 patients, 45 (21.0%) presented with cytological abnormalities (atypical squamous cells of undetermined significance, 13.5%; low-grade squamous intraepithelial lesion, 5.6%; high-grade squamous intraepithelial lesion, 1.9%). Anoscopy was performed in 31 patients (14.4%) and 2 patients (0.9%) had abnormal findings. One case (0.5%) of low-grade anal intraepithelial neoplasia was identified. Only immunosuppression (p = .01) and smoking status (p = .02) were significantly correlated with positive anal cytology results. Limitations of the study include the small single-center sample, a lack of controls, the retrospective design, potential survey response biases, and the nonstandardized survey. CONCLUSIONS The incidence of abnormal cytological findings was 21.0%, whereas low-grade anal intraepithelial was confirmed in 0.5% of the patients. There is a higher incidence of cytological abnormalities among immunosuppressed women and smokers.

Invasive anal squamous cell cancer (IAC) is a health crisis for gay, bisexual, and other men who have sex with men (MSM), and for male-to-female transgendered women who have had sex with men (TWSM), especially within the context of HIV-coinfection where risk for invasive malignancy is greatest (1-6). Currently, experts recommend using the Dacron swab for anal cytology (Pap test) specimen collection at annual and semi-annual intervals for HIV-infected and -uninfected MSM, respectively (7, 8). Dacron-swab anal cytology poorly correlates with histological evaluation of disease (9) and while cervical-cytology sampling has informed anal-cytology specimen collection, cervical screening tools may not be appropriate for analcancer screening. For example, cytobrushes with and without spatulas, cytopicks; and cotton, Dacron, rayon, and nylon-flocked (NF)-swab have been evaluated in genital sampling for pathogens, including HPV, and for cervical cytology (10-14). Cytobrushes improved cervical sampling over cotton swabs by 58-76% for detecting endocervical cells in a sample of >800 adult females >29 years of age (14) and are shown superior to Ayers spatulas (10). One report suggests the cytobrush may be effective in anal cytology,(15) but may be uncomfortable in blind sampling (16). The NF-swab is evaluated extensively for respiratory-pathogen and -cytology sampling, yielding more cells and pathogens than other collection protocols (17-20). For example, Daley et al. report >2-fold cell yield of respiratory epithelial cells using NF-over Dacron swabs, and Krech et al. report a 5-fold greater yield of Chlamydia trachomatis, as well as greater HPV yield using NF-over rayon-wrapped swabs in cervicovaginal tissues (17, 21). Further, unsatisfactory cervical cytology findings range from 0.3-10.9% and 0.17-2.7% for specimens preserved using PreservCyt® (Hologic, Inc., Marlborough, Massachusetts) and SurePath™ (TriPath Imaging, Inc., Burlington, N.C.) preservatives, respectively (22-25), whereas the prevalence of unsatisfactory anal cytology specimens may range from 1% to upwards of 14% (26-33). The cervix and the anal canal are distinct anatomical targets that might easily require different sampling tools. The cervix is firm and sampling is more akin to hitting the bulls-eye on a target while the anal canal is soft and folds much like the surface of a deflated balloon. Cervical cytology uses a speculum to visually guide sample collection and the transformation zone (TZ) of the cervix closely approximates the cervical os. The dentate line lies approximately ~5 centimeters proximal to the anal verge, and the anal TZ immediately adjoins it about ~0.5-1 cm, just cephalad (34). Current anal cytology recommendations are to blindly insert a Dacron swab through the anal verge ~5 cm, approximate it to the anal wall, and rotate the swab using lateral pressure to sample the canal circumferentially as it is withdrawn over 10-20 seconds and stored in liquid preservative for laboratory examination (35). Although experts suggest screening in high-risk populations is important and data show it is cost-effective, there is no current national consensus for screening methods or frequency for anal cancer screening using Papanicolaou staining (Pap test) (8, 36-38). To date, no large studies evaluate the risks or benefits of early detection and treatment for preventing anal cancer and general reluctance among clinicians for anal cytology screening may be due to the imprecision of the test, the rarity of malignancy, and the limited success of available treatments, especially within the context of HIV infection where there is poor control over HPV infections (39-41). Developing a screening strategy with modest-to-high sensitivity and specificity for anal precancers, high-grade anal intraepithelial neoplasia (HG-AIN), is an important public health goal. Thus, to evaluate the sensitivity and specificity for two cytology collection procedures and compare their efficacy for predicting HG-AIN, we evaluated a protocol using an NF-swab (Copan Diagnostics Inc., Murrieta, CA) and the Dacron swab (Thermo Fisher Scientific, Miami, OK), each with preservative, for anal cytology.

OBJECTIVE Anal cancer rates have increased in HIV+ patients. The prevalence of anal intraepithelial neoplasias (AINs) and progression to anal cancer in HIV+ men who have sex with men has been well described, and screening is cost-effective. Our objective was to determine whether anal cancer screening in HIV+ women is cost-effective. MATERIALS AND METHODS A Markov model analysis of 100 HIV+ women was constructed. All women had a CD4 count less than 200 and were assumed to be on antiretrovirals. Rates of AIN were based on previous studies. Progression rates were extrapolated from previous data on HIV+ men who have sex with men. The 5-year model included 3 screening approaches: none, annual, and biennial. Anoscopy and biopsy were performed after an abnormal cytologic result. Low-grade AIN was followed with repeat cytology, and high-grade AIN was treated surgically. Anal cancer was treated surgically followed by chemotherapy and radiation. Sensitivity analyses (SAs) were performed to account for variable rates of AIN progression, anal cancer mortality, and anal cancer and HIV quality-adjusted life years. RESULTS The incremental cost-effectiveness ratio of biennial anal cancer screening compared to no screening was $34,763. Cost-effectiveness was maintained across all assumptions in SA except for decreased progression rate of high-grade AIN to anal cancer. CONCLUSIONS Biennial anal cancer screening in HIV+ women with CD4 counts less than 200 is cost-effective. Annual screening was not cost-effective, likely because of the slow progression of AIN to anal cancer. Further data on rates of AIN progression in HIV+ women based on CD4 count are needed to determine whether screening is cost-effective in women with higher CD4 counts.

OBJECTIVE Medical providers have initiated anal cytology screening among women to detect anal neoplasia early. Lack of knowledge of the human papillomavirus (HPV) and anticipated screening discomfort may limit patient acceptance. This study investigates attitudes toward anal cytology screening among women. MATERIALS AND METHODS Women seen for gynecologic care at an urban university medical center were invited to complete an anonymous survey assessing their understanding of HPV and interest in anal cytology screening. Subjects reported the level of pain, discomfort, and embarrassment they expected from screening on a 100-mm visual analog scale. RESULTS Four hundred four women with mean (SD) age 36 (13) years met criteria for participation. Three hundred thirty-five women reported their race: 52% were white and 36% were African American. Three hundred forty-eight women reported their ethnicities: 76% were Hispanic and 12% were Haitian. Twenty-two percent had never heard of HPV, 57% were not familiar with anal cytology screening, 67% acknowledged that screening was very helpful in detecting anal neoplasia early, and 28% were very interested in undergoing screening. Mean (SD) level of anticipated pain, discomfort, and embarrassment during screening was 62 (32), 68 (30), and 58 (34) mm, respectively. Level of familiarity with anal cytology screening (p < .001), belief in its utility in detecting anal neoplasia (p < .001), and level of anticipated pain (p = .004) were significant predictors of acceptability. CONCLUSIONS Medical providers should improve counseling about anal cytology screening among at-risk women to familiarize them with the procedure, describe its role in detecting anal neoplasia, and address expectations surrounding pain to increase its acceptability.

HPV 6 and 11 cause greater than 90% of genital warts in males and females. Data show that approximately 3–4 million cases of genital warts in men occur each year with a peak rate of 500 per 100,000 in the 25–29 year old group. (1) The majority of these genital warts are diagnosed in men under the age of 30 years. In addition to genital warts, men are at risk for several HPV-related morbidities including penile, anal and oral cancers.

Infection with HIV increases risk of persistent human papillomavirus (HPV) infection and related diseases, including genital warts, cervical cancer, and anal cancer [1–3]. Men who have sex with men have markedly high rates of HPV-related disease including anal cancer, mainly attributable to the high prevalence of HPV infection [4–6] and HIV infection [7, 8]. The advent of highly active antiretroviral therapy has not reduced the high incidence of HPV-related cancers in HIV-infected individuals [9, 10]. Given gay men’s elevated risk for HPV-related diseases, primary prevention efforts such as HPV vaccination and secondary prevention strategies such as anal cancer screening may be particularly beneficial to them [11]. Since the approval of a quadrivalent HPV vaccine (HPV4) for females in 2006 [12], interest in expanding vaccine coverage to males has steadily increased [13–16]. In October 2009, the US Food and Drug Administration approved HPV4 for use by males aged 9 to 26 years [17], although off-label usage would permit men older than 26 years to receive the vaccine as well. Infection with HPV often happens soon after sexual debut, but it is unlikely that sexually active adult men have been exposed to all 4 HPV types present in the quadrivalent vaccine [18]. To understand the role that HIV status may play in HPV prevention efforts, we examined HPV-related knowledge, attitudes, and beliefs in a national sample of gay men.

OBJECTIVE High-resolution anoscopy (HRA) is a useful screening tool for anal intraepithelial neoplasia (AIN), although reputedly challenging for interpretation of suspected lesions. MATERIALS AND METHODS All consecutive patients who underwent biopsies for at least 1 lesion suspicious for AIN during HRA from November 2010 to March 2012 were prospectively included. The characteristics (borders, staining with acetic acid and Lugol iodine solution, and patterns of epithelium and vascularization) of the lesions detected during HRA were compared with histology. RESULTS A total of 168 suspicious anal lesions were biopsied and analyzed in 103 patients (68% men, mean age ± standard deviation = 49.8 ± 9 y, 57% positive status on human immunodeficiency virus infection). According to histology, 41.7% of the lesions were high grade, 34.5% were low grade, and 23.8% were nondysplastic. Lesions with irregular epithelial pattern (or irregular vascularization) were twice as likely to be high grade compared with lesions with regular epithelial pattern (or regular vascularization). The incidences of acetic acid-induced whitening were 91.4%, 94.8%, and 70% among the high-grade AIN, low-grade AIN, and nondysplastic samples, respectively. Among the high-grade AIN, 62.9% were not stained by Lugol solution (vs 31% of the low-grade AIN). The positive predictive value of a combination of these simple morphological criteria was 68.6%. CONCLUSIONS Several simple morphological criteria are significantly associated with high-grade AIN and are found less often in low-grade AIN. A combination of these morphological criteria provides sufficient positive predictive value to guide biopsy placement during HRA.

Objective. This study aimed to assess the prevalence of, and associated factors with, anal intraepithelial neoplasia (AIN) among HIV-positive men evaluated at public health services in Brazil. Materials and Methods. This is a multicenter crosssectional study of HIV-positive male patients attending 6 public AIDS referral clinics in urban Brazil. Participants were interviewed for sociodemographic and behavioral characteristics. Anal swab specimens were collected for anal cytology and HPV DNA testing using L1 polymerase chain reaction. Univariate and multivariate analyses were performed to evaluate risk factors associated with the presence of low-grade squamous intraepithelial lesion (LSIL) and/or high-grade squamous intraepithelial lesion (HSIL). Results. Anal swabs were collected from 343 participants. Prevalence of LSIL/HSIL was 24.8%. The majority (60.1%) reported sexual intercourse with both men and women in their lifetime. At least 36.7% had 1 or more oncogenic HPV types. Four variables were independently associated with the presence of LSIL/HSIL in multivariate analysis: history of sex with both men and women (odds ratio [OR] = 4.8) or men only (OR = 6.2) compared with those having sex with women only; current cigarette smoking (OR = 2.2); current CD4+ level between 200 and 500 cells/mm3 (OR = 2.9) or below 200 cells/mm3 (OR = 3.8) compared with CD4+ level above 500 cells/mm3; and presence of oncogenic anal HPV infection (OR = 9.6). Conclusions. We found a high prevalence of AIN among HIV-positive men in Brazil. This population may serve as an important bridge population to women with implications for anogenital HPV infection in both men and women. Our findings confirm the need to assess screening programs for AIN among high-risk groups, similar to those used to prevent cervical cancer.

This study aimed to conduct a representative survey of human papillomavirus (HPV) prevalence and its genotype distribution in invasive anal cancer specimens in the United States.Population-based archival anal cancer specimens were identified from Florida, Kentucky, Louisiana, and Michigan cancer registries and Surveillance, Epidemiology, and End Results (SEER) tissue repositories in Hawaii, Iowa, and Los Angeles. Sections from 1 representative block per case were used for DNA extraction. All extracts were assayed first by linear array and retested with INNO-LiPA if inadequate or HPV negative.Among 146 unique invasive anal cancer cases, 93 (63.7%) were from women, and 53 (36.3%) were from men. Human papillomavirus (any type) was detected in 133 cases (91.1%) and 129 (88.4%) contained at least 1 high risk-type, most (80.1%) as a single genotype. Human papillomavirus type 16 had the highest prevalence (113 cases, 77.4%); HPV types 6, 11, 18, and 33 were also found multiple times. Among HPV-16-positive cases, 37% were identified as prototype variant Ep, and 63% were nonprototypes: 33% Em, 12% E-G131G, 5% Af1, 4% AA/NA-1, 3% E-C109G, 3% E-G131T, 2% As, and 1% Af2. No significant differences in the distributions of HPV (any), high-risk types, or HPV-16/18 were seen between sex, race, or age group.The establishment of prevaccine HPV prevalence in the United States is critical to the surveillance of vaccine efficacy. Almost 80% of anal cancers were positive for the vaccine types HPV-16 or HPV-18, and in 70%, these were the only types detected, suggesting that a high proportion might be preventable by current vaccines.

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.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.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.Screening procedures for anal HPV-related disease were well tolerated, and no single procedure or HPV sampling device reduced patient compliance.

This study aimed to determine the prevalence of anal intraepithelial lesions in women with histologic diagnosis of intraepithelial lesions of the lower genital tract.This was a cross-sectional study conducted at the Lower Genital Tract and Colposcopy Unit of Hospital de Clínicas "José de San Martín," University of Buenos Aires, Argentina. A total of 481 women with histologically confirmed low-grade and high-grade cervical, vaginal, or vulvar intraepithelial lesions were evaluated between 2005 and 2011. They were referred for cytologic samples and examination with high-resolution anoscopy. We obtained biopsy specimens of any suspicious colposcopic images.Of a total of 481 patients, 404 (84%) were immunocompetent, 31 (6.4%) were HIV+, and 46 (9.6%) had other causes of immunosuppression. Moreover, of the 481 patients, 134 (27.86%) had anal intraepithelial neoplasia (AIN); 28 (5.82%) had high-grade AIN and 106 (22%) had low-grade AIN. Women with high-grade cervical intraepithelial neoplasia (CIN 2, 3) had 2 times the odds of developing AIN compared with women with low-grade CIN (CIN 1) (odds ratio = 1.91, 95% confidence interval = 1.1-3.6). Regarding localization, we found statistically significant difference between the frequency of vulvar and anal lesions. Women with vulvar condylomata and vulvar intraepithelial neoplasia (VIN) may be more likely to develop AIN.Immunocompetent women with CIN, vaginal intraepithelial neoplasia, or VIN may also present high-grade or low-grade anal intraepithelial lesions so we should consider AIN as part of multicentric disease of the lower genital tract. Cervical intraepithelial neoplasia, VIN, condyloma accuminatta, and vaginal intraepithelial neoplasia could be warning signs of anal intraepithelial lesions.

Evaluation of anal intraepithelial neoplasia (AIN) is subjective. Previous studies have shown p16 and Ki-67 expressions to correlate with AIN grade. Biomarkers like p16 and Ki-67 may improve interobserver agreement. The objectives were (1) to determine the extent of interobserver agreement in evaluating AIN on routine hematoxylin and eosin (HE) sections and (2) to test whether p16 and/or Ki-67 staining improve interobserver diagnostic agreement.Seventy-seven anal specimens were retrieved. Sections were stained with monoclonal antibodies against p16 and Ki-67. Blind to the original diagnoses, 4 pathologists assessed HE alone, p16 alone, Ki-67 alone, and all 3 simultaneously. Diagnoses were normal/reactive, AIN I/HPV, AIN II, and AIN III. Agreement was calculated using kappa and S statistics.Pathologists were board certified and had 2 to 25 years (mean = 13.6 years) of experience. Fair agreement was observed using HE diagnosis alone (kappa = 0.38, S = 0.56). The p16 diagnostic evaluation demonstrated the highest agreement (kappa = 0.57, S = 0.73). Interobserver agreement for Ki-67 alone and for HE/p16/Ki-67 combined were comparable to that of HE alone (kappa = 0.4, S = 0.54 and kappa = 0.44, S = 0.62, respectively). When the pathologists' diagnoses for all diagnostic evaluations were compared with consensus diagnoses, the lowest average magnitude of disagreement was seen with Ki-67 alone, followed by p16 alone, HE/p16/Ki-67 combined, and HE alone.Interobserver agreement for diagnosis of AIN was fair when based solely on HE preparation. p16 alone improved interobserver agreement and demonstrated superior agreement when compared with HE, Ki-67, and HE/p16/Ki-67 combined.

Objectives. To determine men's attitudes toward receiving the human papillomavirus (HPV) vaccine. Materials and Methods. Five hundred seventy-one men read a 1-page informational sheet about HPV and the HPV vaccine before completing a 29-item questionnaire. Descriptive statistics were calculated on all variables. Results. Of these men, 33% wanted to receive the HPV vaccine, 27% did not, and 40% were undecided. The main reasons for wanting the vaccine included a desire to stay healthy (67.4%); prevention of cancer in my sexual partner(s) (52.9%); prevention of anal, penile, and head and neck cancer (41.0%); fear of cancer (33.4%); and prevention of genital warts (32.8%). Being in a monogamous relationship and not at risk (18.9%), not interested (13.8%), and not enough evidence yet to prove that it will help men (8.2%) were the main reasons for not wanting to be vaccinated. Conclusions. Although many men want to receive the HPV vaccine, more remain undecided. Pending favorable safety and efficacy results from a clinical trial for men, substantial factual education will likely convince many ambivalent men to receive the HPV vaccine.

Objective The Home Study Course is intended for the practicing colposcopist or practitioner who is seeking to develop or enhance his or her colposcopic skills. The goal of the course is to present colposcopic cases that are unusual or instructive in terms of appearance, presentation, or management, or that demonstrate new and important knowledge in the area of colposcopy or pathology. Participants may benefit from reading and studying the material or from testing their knowledge by answering the questions. Accme accreditation The American Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The ASCCP designates this continuing medical education activity for 1-hour Category I credit of the Physician's Recognition Award of the American Medical Association and 1-hour Category I credit of the ASCCP's Program for Continuing Professional Development. Credit is available for those who choose to apply. The Home Study Course is planned and produced in accordance with the ACCME's Essential Areas and Elements.

HPV associated cervical transformation is characterized by well-defined steps, including persistent HPV infection and deregulated oncogene expression. Recent studies have suggested that a number of lower genital tract lesions are clonally related to cervical lesions. In the current study, HPV infections and oncogene expression were assessed in a large series of patients with multicentric lower genital tract disease to analyze the transformation steps in extracervical disease.One hundred and thirty biopsies of 52 women treated for multicentric synchronous or metachronous lower genital tract intraepithelial neoplasias were collected. Up to seven multicentric specimens taken from one patient were studied with a maximum follow up of 20 years. HPV typing and p16(ink4a) immunostaining was performed.HPV DNA was present in 121 of 130 specimens (93%). HPV16 was frequently found in VIN, VaIN and AIN (73, 60 and 77%, respectively), whereas only 37% of CIN were HPV16 positive. Infections with identical HPV types in multicentric lesions were diagnosed in 46% of the HPV positive patients. p16INK4a expression was negative in the nine HPV negative lesions whereas about 90% of the high grade lesions showed diffuse p16 staining.Our findings indicate that multicentric lower genital tract disease evolves through different pathways. Some cases were related to a high susceptibility towards HPV infections, while others exhibited features of clonal propagation of transformed cervical cell clones. The clinical management of the latter group is particularly challenging, because malignant cell clones can persist over a long time course.

The objective of this study was to determine the clinical effectiveness of a prime-boost human papillomavirus (HPV) vaccine regimen. A nonrandomized phase II prime-boost vaccine trial was conducted. Women with biopsy-proven anogenital intraepithelial neoplasia (AGIN) 3 were vaccinated with three doses of a recombinant fusion protein comprising HPV 16, E6/E7/L2 (TA-CIN) followed by one dose of a recombinant vaccinia virus encoding HPV 16 and 18 E6/E7 (TA-HPV). Clinical responses were evaluated by serial photographs, symptomatology, and biopsies before and after vaccination. Twenty-nine women were vaccinated; 27 with vulval intraepithelial neoplasia 3 and 2 with vaginal intraepithelial neoplasia grade 3. Clinical responses were seen in five women (17%), with one complete and five partial responses. Fifteen women (62%) had symptomatic improvement. No serious adverse effects were recorded. This is the first trial of a prime-boost vaccination regimen using heterologous HPV vaccines (TA-CIN followed by TA-HPV) in the management of AGIN. Since the prime-boost approach in this cohort offered no significant advantages over single TA-HPV vaccination, there are no further studies planned using this protocol. Future studies are warranted to define responders to immunotherapy.