Prevention Of Anal Cancer Research Articles

Santé anale et fin annoncée du sida : un impensé de la sexualité et des risques chez les hommes ayant des relations sexuelles avec des hommes

The Prevanal study is interested in anal cancer in MSM: a rare cancer linked in 90 % of cases to an infection with the human papillomavirus (HPV). Sexually transmitted despite the use of a condom, it affects in particular HIV-positive MSM who are considered a particularly exposed group. It aims above all to translate an epidemiological problem into a socio-anthropological question focused on sexuality and gender identities. The challenge is to develop a multidimensional approach to this emerging and resurgent health issue among MSM. In this period of biomedicalization of HIV prevention and the predicted end of AIDS, the notion of pleasure or risk associated with the anus as a sexual organ has remained a blind spot in research and must be placed at the center of investigation and analysis. The cultural dimension of the obstacles to the prevention, diagnosis and care of anal cancer among MSM needs to be documented, while identifying the simultaneous unthought of their sexual desires and their health needs.

Topical Protease Inhibitor Decreases Anal Carcinogenesis in a Transgenic Mouse Model of HPV Anal Disease.

Anal cancer is a major health problem. This study seeks to determine if the topical protease inhibitor Saquinavir (SQV), is effective at the prevention of anal cancer in transgenic mice with established anal dysplasia. K14E6/E7 mice were entered into the study when the majority spontaneously developed high-grade anal dysplasia. To ensure carcinoma development, a subset of the mice was treated with a topical carcinogen: 7,12-Dimethylbenz[a]anthracene (DMBA). Treatment groups included: no treatment, DMBA only, and topical SQV with/without DMBA. After 20 weeks of treatment, anal tissue was harvested and evaluated histologically. SQV was quantified in the blood and anal tissue, and tissue samples underwent analysis for E6, E7, p53, and pRb. There was minimal systemic absorption of SQV in the sera despite high tissue concentrations. There were no differences in tumor-free survival between SQV-treated and respective control groups but there was a lower grade of histological disease in the mice treated with SQV compared to those untreated. Changes in E6 and E7 levels with SQV treatment suggest that SQV may function independently of E6 and E7. Topical SQV decreased histological disease progression in HPV transgenic mice with or without DMBA treatment without local side effects or significant systemic absorption.

Human Papillomavirus-Associated Anal Cancer Incidence and Burden Among US Men, According to Sexual Orientation, Human Immunodeficiency Virus Status, and Age.

Men who have sex with men (MSM) without HIV are known to be at elevated relative risk for Human papillomavirus (HPV)-associated anal cancer in comparison to men who have sex with women (MSW), but are poorly characterized in terms of anal cancer incidence due to absence of reporting of sexual behavior/identity at a population-level. By combining age-specific statistics from multiple data sources (anal cancer incidence among all males; anal cancer incidence among MSM and MSW with HIV; population size of men with HIV by sexual orientation), we developed a mathematical model to estimate anal cancer incidence, annual number of cases, and proportion by (a) sexual orientation (MSM versus MSW), (b) HIV status, and (c) age (<30, 30-44, 45-59, and ≥60 years). Anal cancer incidence (per 100 000) among MSM without HIV was 1.4 (95% uncertainty interval [UI], 0.6 to 2.3), 17.6 (95% UI = 13.8-23.5), and 33.9 (95% UI = 28.3-42.3), at ages 30-44, 45-59 and ≥60 years, respectively. 19.1% of all male anal cancer occurred in MSM without HIV, increasing from 4% of anal cancer diagnosed at 30-44 years to 24% at ≥60 years; 54.3% occurred in MSW without HIV (increasing from 13% at age 30-44 to 67% at >60 years), and the remaining 26.6% in men (MSM and MSW combined) with HIV (decreasing from 83% at age 30-44 to 9% at >60 years). These findings should inform anal cancer prevention recommendations in male risk groups, including, for the first time, for the important group of MSM without HIV.

Risk assessment and the prevention of anal cancer among people living with HIV

Risk assessment and the prevention of anal cancer among people living with HIV

Effect of the introduction of screening for cancer precursor lesions on anal cancer incidence over time in people living with HIV: a nationwide cohort study

Incidence of anal cancer is high in people living with HIV, particularly in men who have sex with men (MSM). Screening for and treatment of precursor lesions might prevent progression to anal cancer in people living with HIV. We examined trends in incidence of and mortality after anal cancer diagnosis in people living with HIV, including the effect of screening from 2007 onwards, in the Netherlands. In this observational cohort study, we analysed data from the ongoing open nationwide Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort. We included all consenting adults living with HIV and identified all primary anal squamous cell carcinoma. We reported temporal trends in incident anal cancer cases from Jan 1, 1996, to Dec 31, 2020, and all-cause and anal cancer-related mortality in individuals diagnosed with anal cancer. Multivariable Poisson regression was used to explore risk factors for incident anal cancer and multivariable Cox regression was used to explore risk factors for anal cancer-related mortality. Among 28 175 individuals in HIV care (59·7% MSM), 227 primary anal cancer cases were diagnosed. Despite the increasing average age of the cohort, crude incidence rates of anal cancer in MSM declined slowly over time, from 107·0 (95% CI 75·7-147·0) per 100 000 person-years in 1996-2005 to 93·7 (75·3-115·0) per 100 000 person-years in 2013-20 (p=0·49). Crude incidence rates in men who do not have sex with men (non-MSM) and women were generally lower than in MSM, but increased slightly over time, from 51·08 (95% CI 20·54-105·25) to 67·82 (40·83-105·91; p=0·52) per 100 000 person-years in non-MSM and from 8·09 (0·20-45·06) to 24·95 (10·03-51·40; p=0·29) per 100 000 person-years in women. The age-adjusted incidence rate in MSM in 2013-20 was significantly lower (rate ratio 0·62 [95% CI 0·41-0·92]) compared with in 1996-2005. Changes in risk factors (less smoking, cumulative exposure to CD4 count of <200 cells per μL, and plasma HIV-1 RNA of >1000 copies per mL) mostly explained the decrease in anal cancer risk over time in MSM. 3866 (23·0%) of 16 819 MSM participated in anal cancer screening at least once. TNM tumour staging was more favourable (Cochrane-Armitage test for trend p=0·033) in individuals diagnosed during screening. Crude anal cancer-associated 5-year mortality in people living with HIV decreased from 30·4% (1996-2005) to 18·3% (2013-20; odds ratio 0·48; p=0·070). Anal cancer-related mortality was 3·7% (95% CI 0·5-23·5) in all men who had been screened and 24·0% (95% CI 18·1-31·3) in men who had not been screened (p=0·023). In men, screening participation (hazard ratio [HR] 0·31, p=0·051) and cumulative exposure to CD4 counts of less than 200 cells per μL (HR 1·11 per year; p=0·0022) were independently associated with anal cancer-related mortality. As anal cancer incidence is slowly declining in MSM but not in non-MSM and women, health-care professionals should not focus only on MSM for anal cancer prevention. Men diagnosed with anal cancer during screening had improved survival, probably because they were diagnosed at an earlier disease stage. Next to preventing anal cancer, these data are an important justification to screen those most at risk of anal cancer. None.

Performance of Human Papillomavirus Attribution Algorithms to Predict Causative Genotypes in Anal High-Grade Lesions.

Gay and bisexual men (GBM) are at increased risk of human papillomavirus (HPV)-associated anal high-grade squamous intraepithelial lesions (HSILs). Understanding the fractions of HSILs attributable to HPV genotypes is important to inform potential impacts of screening and vaccination strategies. However, multiple infections are common, making attribution of causative types difficult. Algorithms developed for predicting HSIL-causative genotype fractions have never been compared with a reference standard in GBM. Samples were from the Study of the Prevention of Anal Cancer. Baseline HPV genotypes detected in anal swab samples (160 participants) were compared with HPV genotypes in anal HSILs (222 lesions) determined by laser capture microdissection (LCM). Five algorithms were compared: proportional, hierarchical, maximum, minimum, and maximum likelihood estimation. All algorithms predicted HPV-16 as the most common HSIL-causative genotype, and proportions differed from LCM detection (37.8%) by algorithm (with differences of -6.1%, +20.9%, -20.4%, +2.9%, and +2.2% respectively). Fractions predicted using the proportional method showed a strong positive correlation with LCM, overall (R = 0.73 and P = .002), and by human immunodeficiency virus (HIV) status (HIV positive, R = 0.74 and P = .001; HIV-negative, R = 0.68 and P = .005). Algorithms produced a range of inaccurate estimates of HSIL attribution, with the proportional algorithm performing best. The high occurrence of multiple HPV infections means that these algorithms may be of limited use in GBM.

Abstract B052: Integrating HPV (human papillomavirus) vaccination into HIV prevention: Acceptability and information needs among PrEP (pre-exposure prophylaxis) patients at a federally qualified health center

Abstract Background: Anal cancer disproportionally impacts gay, bisexual, and other male sexual minorities (GBM). Human Papillomavirus (HPV) vaccination is a safe and effective method to prevent anal cancer; however, coverage of HPV vaccination among adult GBM is low. Key barriers to vaccination are lack of awareness and knowledge of anal cancer, low motivation to get vaccinated, and lack of access and availability. For many young GBM, regular interactions with the healthcare system center around HIV prevention. Thus, we propose that federally qualified health centers (FQHCs) can increase uptake and reach of HPV vaccination by integrating and promoting HPV vaccination in ongoing HIV preventive care (e.g., Pre-exposure Prophylaxis [PrEP]). The objectives of this project were to (1) assess the acceptability of integrating HPV vaccination with PrEP management and (2) determine needs for informed decision making. Methods: We conducted a web-based cross-sectional survey of unvaccinated GBM (18-45) who received PrEP care at a FQHC in Philadelphia. Data collection took place in 2021 and 2022. The main outcome was intent to initiate HPV vaccination within 12 months (5-point scale). Other measures included beliefs about HPV vaccination in PrEP care, perceived information needs, and preferred information delivery modes. Descriptive and bivariate statistics were used to analyze the data. Results: The sample (N=59) was ethnoracially diverse (50.0% non-White) and in the catchup (23.7%; 18-26 yrs.) or shared clinical decision making (76.3%; 27-45) age ranges. Most were gay identified (71.2%) cisgender men (74.6%). Just 23.7% were aware they were eligible for HPV vaccination and even fewer knew that vaccination could prevent anal cancer (11.9%). Overall vaccine intentions were high (M=3.7; SD=1.0). Intentions were 26.1% higher (M=4.4; SD=1.0) if HPV vaccination was offered during PrEP appointments. Most (88.7%) agreed that offering HPV vaccination during PrEP visits would increase the likelihood that they would get vaccinated; however, 64.4% strongly/somewhat agreed that they needed more information about HPV vaccination prior to making an informed decision. Perceived information need was inversely associated with vaccine intentions (r=-0.31, p=0.02). Most participants (&amp;gt;50%) indicated they wanted to know more about their risk for anal cancer and effectiveness of HPV vaccination. The majority (71.2%) preferred to get medically accurate information on anal cancer prevention from a website that they could go to on their own time. Other delivery modes were iPads at their doctor’s office (28.8%), printed information given to them by their doctor (28.8%), and text messages from a healthcare provider (25.4%). Conclusion: Offering and promoting HPV vaccination as part of PrEP management visits was highly acceptable among PrEP patients. Interventions should focus on raising awareness about anal cancer and promoting informed decision making for anal cancer prevention. Citation Format: Christopher W. Wheldon, Sarah Bass, Bradley Collins. Integrating HPV (human papillomavirus) vaccination into HIV prevention: Acceptability and information needs among PrEP (pre-exposure prophylaxis) patients at a federally qualified health center [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B052.

Incidence of abnormal anal cytology in HIV-infected and HIV-uninfected men who have sex with men.

Anal cytology is used in the prevention of anal cancer, which disproportionally affects men who have sex with men (MSM). Data on the incidence of cytologic abnormalities in these individuals are scant. MSM with baseline negative anal cytology and at least one further adequate cytology were included. Incidence rate for positive atypical squamous cells of undetermined significance (ASC-US+) was calculated. Kaplan-Meier curves were compared by log-rank test according to HIV status, baseline high-risk human papillomavirus (HPV) (high-risk HPV-negative, HPV16-positive, other high-risk HPV-positive [non-HPV16]) and high-risk HPV persistence (positive from baseline to the first ASC-US+or last visit for those who remained cytologically negative). Cox univariate and multivariate analyses were performed. A total of 250 MSM were included: 52/153 (34.0%) HIV-uninfected MSM had an ASC-US+report at follow-up (incidence: 13.1 × 100 person-years; 95% CI, 9.8-17.2); 48/97 (49.5%) HIV-infected MSM developed cytologic abnormalities (incidence: 16.0 × 100 person-years; 95% CI, 11.8-21.2). ASC-US+incidence in HIV-uninfected and HIV-infected MSM did not differ significantly (p=.32). Kaplan-Meier curves did not differ significantly according to baseline high-risk HPV. Differences were significant between those with and without persistent high-risk HPVs, both among HIV-uninfected (p=.03) and HIV-infected MSM (p=.008). Age (adjusted hazard ratio [aHR], 0.98; 95% CI, 0.96-0.99), high-risk HPV persistence (aHR, 1.57; 95% CI, 1.02-2.39), and condomless receptive anal sex (aHR, 1.99; 95% CI, 1.31-3.03) were predictors for incident ASC-US+. Despite the limited number of subjects, in our study HIV-uninfected and HIV-infected MSM have a similar ASC-US+incidence. Occurrence of ASC-US+ was significantly affected by age, high-risk HPV persistence, and condomless receptive anal sex. The assessment of HPV persistence might identify those MSM at higher risk for anal lesions.

Automated In Vivo High-Resolution Imaging to Detect Human Papillomavirus-Associated Anal Precancer in Persons Living With HIV.

In the United States, the effectiveness of anal cancer screening programs has been limited by a lack of trained professionals proficient in high-resolution anoscopy (HRA) and a high patient lost-to-follow-up rate between diagnosis and treatment. Simplifying anal intraepithelial neoplasia grade 2 or more severe (AIN 2+) detection could radically improve the access and efficiency of anal cancer prevention. Novel optical imaging providing point-of-care diagnoses could substantially improve existing HRA and histology-based diagnosis. This work aims to demonstrate the potential of high-resolution microendoscopy (HRME) coupled with a novel machine learning algorithm for the automated, in vivo diagnosis of anal precancer. The HRME, a fiber-optic fluorescence microscope, was used to capture real-time images of anal squamous epithelial nuclei. Nuclear staining is achieved using 0.01% wt/vol proflavine, a topical contrast agent. HRME images were analyzed by a multitask deep learning network (MTN) that computed the probability of AIN 2+ for each HRME image. The study accrued data from 77 people living with HIV. The MTN achieved an area under the receiver operating curve of 0.84 for detection of AIN 2+. At the AIN 2+ probability cutoff of 0.212, the MTN achieved comparable performance to expert HRA impression with a sensitivity of 0.92 ( P = 0.68) and specificity of 0.60 ( P = 0.48) when using histopathology as the gold standard. When used in combination with HRA, this system could facilitate more selective biopsies and promote same-day AIN2+ treatment options by enabling real-time diagnosis.

Conventional cytologic diagnosis of human papillomavirus-induced anal intraepithelial neoplasia: The experience of a referral center in Rio de Janeiro, Brazil.

Screening of anal cancer is rarely available or performed in Brazil. This study analyzes the diagnostic performance of conventional cytology (CC) in the prevention of anal cancer in a coloproctology and gynecology outpatient clinics in a public hospital in Rio de Janeiro, Brazil. From 2005 to 2017, 1066 conventional cytological samples were collected. We analyze the causes of unsatisfactory samples (11.3%) and compare the cytological diagnoses of 83 samples from persons living with HIV and persons not living with HIV and in specific situations, using as the gold standard high-resolution anoscopy or histopathology in cases biopsied within 6 months after cytology. The sensitivity of cytology with diagnosis of ASC-US for detection of anal intraepithelial neoplasia of any grade was 85%, specificity was 41%, positive and negative predictive values were 64% and 75%, respectively, and positive and negative likelihood ratios were 1.46 and 0.35, respectively. Conventional cytology available in resource-limited settings is a simple, noninvasive, low-cost method that proved feasible for outpatient screening of precursor lesions of the anal canal.

Anal Cancer Prevention Through the Topical Use of Single or Dual PI3K/mTOR Inhibitors

IntroductionAnal dysplasia and anal cancer are major health problems. This study seeks to determine if inhibition of mTOR and/or PI3K pathways is effective at anal cancer prevention in mice with/without established precancerous lesions of the anus (anal dysplasia). MethodsK14E6/E7 mice were entered into the study at 5 wk, 15 wk, or 25 wk of age. Mice were treated with a topical carcinogen, 7,12-Dimethylbenz[a]anthracene (DMBA), which ensures carcinoma development within 20 wk. Treatment groups included: no treatment, DMBA only, topical Pictilisib (PI3K inhibitor) with/without DMBA, topical Sapanisertib (mTOR inhibitor) with/without DMBA, and topical Samotolisib (dual PI3K/mTOR inhibitor) with/without DMBA. Mice underwent weekly observations for anal tumor development (tumor-free survival). After 20 wk of treatment, anal tissue was harvested and evaluated histologically for squamous cell carcinoma (SqCC). ResultsAll topical treatments in conjunction with DMBA increased tumor-free survival in mice that started treatment at 15 wk of age when compared to DMBA-only treatment, except for Pictilisib + DMBA in males. Topical Sapanisertib increased tumor-free survival in mice regardless of starting treatment age. When examining tissue for microscopic evidence of SqCC, only topical Samotolisib in males decreased SqCC in the 15 wk starting mice. ConclusionsSapanisertib, the mTOR inhibitor, had the greatest effect, in terms of increasing tumor-free survival, regardless of starting time point or sex. Unlike the other treatments, Samotolisib, the dual PI3K/mTOR inhibitor, decreased microscopic evidence of SqCC when starting treatment at 15 wk of age but only in male mice.

Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies.

Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized. We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection. This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.

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

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

Uptake of Human Papillomavirus Vaccination by HIV Status and HIV Pre-exposure Prophylaxis (PrEP) Care Engagement Among Young Sexual Minority Men 17-24 Years Old in the USA.

HIV and human papillomavirus (HPV) are common sexually transmitted infections among young sexual minority men (YSMM) that are prevented by pre-exposure prophylaxis (PrEP) and HPV vaccination, respectively. We sought to determine the association between a history of PrEP use and HPV vaccination uptake among YSMM. Data were collected from an online survey of YSMM (n = 287; M age = 20.6 years, range: 17-24; 58% Black or Latinx) recruited from social media and men-for-men geosocial networking apps in 2020 and analyses were conducted using chi-squared comparisons and Poisson regression using STATA (IC) version 15.1. About half (45.0%) of YSMM reported receiving at least one dose of the HPV vaccine. Controlling for other factors, YSMM who were living with HIV or had used PrEP were significantly more likely to have received at least one dose of an HPV vaccine (PR = 2.48, 95% CI = 1.52-4.07; PR = 1.70, 95% CI = 1.26-2.31, respectively). YSMM living with HIV or with PrEP use experience reported higher rates of HPV vaccination compared to their counterparts, potentially due to greater utilization of health care or contacts with providers attuned to their health needs. Nevertheless, HPV vaccination uptake is suboptimal given the high prevalence of high-risk HPV genotypes among YSMM. Standard of care for YSMM should include revisiting HPV vaccination status and discussion of PrEP and other HIV prevention methods given suboptimal rates of HPV and PrEP uptake among this priority population for HPV vaccination, anal cancer, and HIV prevention.

Update on the Epidemiological Features and Clinical Implications of Human Papillomavirus Infection (HPV) and Human Immunodeficiency Virus (HIV) Coinfection.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI) worldwide. Although most HPV infections will spontaneously resolve, a considerable proportion of them will persist, increasing the risk of anogenital dysplasia, especially within certain populations, such as patients infected with human immunodeficiency virus (HIV). Furthermore, high-risk oncogenic HPV types (HR-HPV) are the main cause of cervix and other anogenital cancers, such as cancer of the vagina, vulva, penis, or anus. HIV and HPV coinfection is common among people living with HIV (PLWH) but disproportionally affects men who have sex with men (MSM) for whom the rate of persistent HPV infection and reinfection is noteworthy. The molecular interactions between HIV and HPV, as well as the interplay between both viruses and the immune system, are increasingly being understood. The immune dysfunction induced by HIV infection impairs the rate of HPV clearance and increases its oncogenic risk. Despite the availability of effective antiretroviral therapy (ART), the incidence of several HPV-related cancers is higher in PLWH, and the burden of persistent HPV-related disease has become a significant concern in an aging HIV population. Several public health strategies have been developed to reduce the transmission of HIV and HPV and mitigate the consequences of this type of coinfection. Universal HPV vaccination is the most effective preventive tool to reduce the incidence of HPV disease. In addition, screening programs for HPV-related cervical and vulvovaginal diseases in women are well-recognized strategies to prevent cervical cancer. Similarly, anal dysplasia screening programs are being implemented worldwide for the prevention of anal cancer among PLWH. Herein, the main epidemiological features and clinical implications of HIV and HPV coinfection are reviewed, focusing mainly on the relationship between HIV immune status and HPV-related diseases and the current strategies used to reduce the burden of HPV-related disease.

Anal Cancer Screening and Prevention: Summary of Evidence Reviewed for the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infection Guidelines.

In June 2019 the Centers for Disease Control and Prevention (CDC) convened an advisory group to assist in development of the 2021 CDC sexually transmitted infections (STI) guidelines. The advisory group on anal cancer screening and prevention met to formulate key questions in this field. The group examined published literature and abstracts to assess evidence and give recommendations for development of the CDC guidelines. This article summarizes key questions, evidence, recommendations, and areas for further research for the screening, diagnosis, and prevention of anal cancer.

Age-Specific Prevalence of Anal and Cervical Human Papillomavirus Infection and High-Grade Lesions in 11 177 Women by Human Immunodeficiency Virus Status: A Collaborative Pooled Analysis of 26 Studies.

Age-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention. We centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology. In HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15-24 years to 1.0% at ≥55 years; ptrend = 0.0026) and cervix (7.4% to 1.7%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+. Age-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk.

Temporal Trends and Projection of Cancer Attributable to Human Papillomavirus Infection in China, 2007-2030.

Information on temporal trends of cancer attributable to human papillomavirus (HPV) in China is limited. Cancer incidence and mortality during 2007 to 2015 were extracted from the Chinese Cancer Registry Annual Report and the national population from the National Bureau of Statistics. HPV-attributable cancer burden and the average annual percentage change during 2007 to 2015 were estimated and cancer burden during 2016 to 2030 was projected. HPV-attributable cancer cases have increased by 3.8% [95% confidence interval (CI), 2.9%-4.8%] annually from 85,125 to 113,558 and age-standardized incidence rate (ASIR) rose by 3.0% (95% CI, 2.5%-3.5%) from 4.67 to 5.83 per 100,000 persons during 2007 to 2015. Cervical, female anal, and vulva cancer cases have increased by 3.8% (95% CI, 2.8%-4.7%), 6.5% (95% CI, 1.2%-12.2%), and 3.7% (95% CI, 1.6%-5.8%) per year. Male anal and oropharyngeal cancer cases have elevated by 7.5% (95% CI, 2.8%-12.5%) and 4.4% (95% CI, 2.4%-6.3%) annually. The increases of cervical and anal cancer were most rapid among those aged 50 and older. HPV-attributable cancer deaths and mortality rate have risen by 4.7% (95% CI, 2.9%-6.7%) and 3.3% (95% CI, 0.9%-5.8%) respectively. HPV-attributable cancer cases and ASIR are projected to reach 214,077 and 9.35 of 100,000 persons by 2030 respectively, with 87.7% being cervical cancer, and anal cancer cases are expected to triple. HPV-attributable cancer burden has largely increased in the past and will keep rising for the next decade. Cervical cancer control should be the priority and anal cancer prevention should be addressed. This study supplies fundamental evidence for policy-making on HPV-attributable cancer control.

Possible Reactivation of Latent Anal Human Papillomavirus Associated with Markers of Immune Dysfunction in Gay and Bisexual Men.

It is unknown whether reactivation of human papillomavirus (HPV) after latency occurs in the anus. We measured incidence and predictors of incident anal HPV in sexually inactive gay and bisexual men (GBM) as a surrogate of HPV reactivation. The Study of the Prevention of Anal Cancer collected data on sexual behavior, anal cytology, HPV DNA, histology and HPV serology. HPV incidence during periods when zero sexual partners were reported in the last six months at both the current and previous annual visit ("no sexual activity") was analyzed by Cox regression using the Wei-Lin-Weissfeld method to determine univariable predictors. Of 617 men enrolled, 525 had results for ≥2 visits, of whom 58 (11%) had ≥ one period of "no sexual activity". During sexually inactive periods, there were 29 incident high risk HPV infections in 20 men, which occurred more commonly in older men (Ptrend = 0.010), HIV-positive men (HR = 3.12; 95% CI, 0.91-16.65), longer duration of HIV (Ptrend = 0.028), history of AIDS defining illness (P = 0.010), lower current (P = 0.010) and nadir CD4 count (P = 0.014). For 18 of 29 infections with available results, 12 men remained type-specific HRHPV L1 seronegative. None were consistently seropositive. A new diagnosis of HSIL occurred in only two men, caused by an HPV type other than the incident type. Our findings suggest that in sexually inactive GBM, anal HRHPV incidence is relatively common, and is associated with increasing age and immune dysfunction, a pattern consistent with HPV reactivation. Reactivation of anal HPV may occur.

PI3K/mTOR inhibition prevents anal cancer in mice with established low-grade anal dysplasia

Low-grade anal dysplasia is a disease that can progress to high-grade anal dysplasia and eventually anal cancer if left untreated. Research has shown that low-grade anal dysplasia is marked by significant autophagic dysfunction. We hypothesized that systemic induction of autophagy, via phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR) inhibition, would be effective in preventing anal cancer development in human papillomavirus (HPV) mice (K14E6/E7) with established low-grade anal dysplasia. Mice began treatment at 15 weeks of age, when 75% of mice spontaneously develop low-grade anal dysplasia, and were divided into the following groups: no treatment, systemic LY3023414 (4.5 mg/kg, dual PI3K/mTOR inhibitor) alone, topical 7,12 dimethylbenz[a]anthracene (DMBA) alone, or systemic LY3023414 and topical DMBA. Groups were compared for final histology, PI3K activity, mTOR activity, autophagic induction (light chain 3B (LC3β)), autophagic function (p62 protein), and tumor-free survival. Untreated mice or mice treated with LY3023414 alone did not progress to cancer. There was a statistically significant decrease in the number of mice that developed histologic evidence of cancer when comparing mice that received systemic LY3203414 with topical DMBA versus those that received topical DMBA alone (p = 0.0003). PI3K and mTOR activity decreased in groups treated with systemic LY3023414 and topical DMBA as compared with those treated with topical DMBA alone (p = 0.0005 and p = 0.0271, respectively). LC3β and p62 expression was not statistically altered with systemic LY3023414 treatment. Mice developed less overt tumors and had increased tumor-free survival when treated with systemic LY3023414 in the presence of topical DMBA compared to topical DMBA alone (p = 0.0016 and p < 0.001, respectively). Systemic LY3023414 treatment is effective in anal cancer prevention in the setting of established low-grade anal dysplasia in an HPV-associated mouse model of anal cancer.