Human Papillomavirus and Associated Cancers: A Review.

The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however, persistent infection can result in a wide array of diseases, ranging from genital warts to cancer. Most cases of cervical, anal, and oropharyngeal cancers are due to HPV infection, with cervical cancer being one of the leading causes of cancer death in women worldwide. Screening is available for HPV and cervical cancer, but is not available everywhere, particularly in lower-resource settings. HPV infection disproportionally affects individuals living with HIV, resulting in decreased clearance, increased development of cancer, and increased mortality. The development of the HPV vaccine has shown a drastic decrease in HPV-related diseases. The vaccine prevents cervical cancer with near 100% efficacy, if given prior to first sexual activity. Vaccination uptake remains low worldwide due to a lack of access and limited knowledge of HPV. Increasing awareness of HPV and access to vaccination are necessary to decrease cancer and HPV-related morbidity and mortality worldwide.

The influence of home versus clinic anal human papillomavirus sampling on high-resolution anoscopy uptake in the Prevent Anal Cancer Self-Swab Study.

Background Anal cancer disproportionately affects sexual and gender minority individuals living with HIV. High-resolution anoscopy (HRA) is an in-clinic procedure to detect precancerous anal lesions and cancer, yet prospective data on factors associated with HRA attendance are lacking. We examined whether anal HPV sampling at home versus in a clinic impacts HRA uptake and assessed HRA acceptability. Methods Sexual and gender minority individuals were randomised to home-based self-sampling or clinical sampling. All were asked to attend in-clinic HRA 1year later. We regressed HRA attendance on study arm using multivariable Poisson regression and assessed HRA acceptability using χ 2 tests. Results A total of 62.8% of 196 participants who engaged in screening attended HRA. Although not significant (P =0.13), a higher proportion of participants who engaged in clinic-based screening attended HRA (68.5%) compared to home-based participants (57.9%). Overall, HRA uptake was higher among participants with anal cytology history (aRR 1.40, 95% CI 1.07-1.82), and lower among participants preferring a versatile anal sex position versus insertive (aRR 0.70, 95% CI 0.53-0.91), but did not differ by race or HIV serostatus. In the clinic arm, persons living with HIV had lower HRA attendance (42.9%) versus HIV-negative participants (73.3%) (P =0.02) and Black non-Hispanic participants had lower HRA attendance (41.7%) than White non-Hispanic participants (73.1%), (P =0.04). No differences in attendance by race or HIV status were observed in the home arm. Conclusions HRA uptake differed significantly by race and HIV status in the clinic arm but not the home arm.

Preventive Care for Men Who Have Sex With Men.

Men who have sex with men (MSM) is an inclusive term used to refer to phenotypic males who have insertive or receptive sex (penile-anal or penile-oral) with other phenotypic males, including people who are transgender or have other gender identities. MSM may report their sexual orientation as homosexual, bisexual, heterosexual, or something else, but this stated sexual orientation may not align with their sexual attraction or behaviors. Several health conditions disproportionately affect MSM compared with age-matched heterosexual men, including HIV infection, anal cancer, syphilis, and depression. Clinicians should use culturally sensitive questions to obtain a comprehensive sexual history and assess sexual risk. MSM should receive regular screening for HIV, hepatitis B and C, gonorrhea, chlamydia, and syphilis. Vaccinations for hepatitis A and B and human papillomavirus should be offered. MSM may benefit from preexposure prophylaxis to prevent HIV infection, postexposure prophylaxis to reduce the risk of HIV transmission, and counseling on safer sexual practices. Screening for anal cancer associated with human papillomavirus may be performed by digital anal rectal examination, although the optimal screening strategy has yet to be determined. Clinicians should also consider more frequent screenings for mental health issues in the MSM population because the rates of depression, suicide, substance use, and other psychosocial issues are higher than those of the general population.

A Qualitative Analysis of Knowledge Levels, Perceived Susceptibility, and Perceived Severity Surrounding Anal Cancer and Human Papillomavirus.

INTRODUCTION: When examining health literacy and disease specific knowledge levels across ethnicities and communities, ethnic minority groups are known to be at a higher risk of being below the average health literacy threshold which is a factor linked to poor health status and higher mortality rates. This study examined disease specific knowledge levels, perceived severity, and perceived susceptibility surrounding anal cancer and HPV-related screening behaviors. METHODS: The following research questions were explored: (1) "What are the common themes and/or beliefs when asked about anal cancer, HPV, and preventive screening?" and (2) "What are the common themes and beliefs surrounding the severity and susceptibility of contracting anal cancer?". This study utilized a cross-sectional design to survey 26 individuals regarding their knowledge level and perspectives regarding anal cancer and HPV. An 8-question survey was developed de novo based on an application of the Health Belief Model (HBM) elements. This study employed thematic analysis to explore critical themes to construct a model to understand knowledge levels, attitudes, and risk perceptions regarding anal cancer and intention to participate in preventive screenings. The fundamental attitudes and themes related to anal cancer risk and intention to participate in preventative screenings were elicited using a qualitative descriptive technique. Coded data was utilized to analyze themes based on (1) knowledge and (2) perceived risk, both severity and susceptibility. RESULTS: Overall, the findings indicate very low levels of knowledge regarding screening, anal cancer, and HPV across all genders. The low levels of anal cancer and HPV knowledge were seen in 13 coded segments (50% of surveys) which showed no familiarity with or comprehension of HPV, and 4 coded segments indicated no familiarity with anal cancer. In addition, 15 respondents (57%) had low or no preventive or screening-related knowledge. While some respondents (46%) illustrated high perceived severity for anal cancer, only 23% indicated high perceived susceptibility for anal cancer. CONCLUSION: The results from this study may be used to inform practitioners, providers, and policymakers in developing interventions addressing low levels of understanding and disease specific knowledge surrounding anal cancer in support of creating a standardized health screening procedure.

Acceptability of Anal Human Papillomavirus Home Self-Sampling and Clinician Sampling Among Sexual and Gender Minority Individuals in Milwaukee, Wisconsin: The Prevent Anal Cancer Self-Swab Study.

Purpose: Anal cancer has disproportionately high incidence among sexual minority men. We compared acceptability of home versus clinic human papillomavirus (HPV) anal swabbing. Methods: The Prevent Anal Cancer Self-Swab Study recruited sexual and gender minority individuals in Milwaukee, Wisconsin. Eligible participants were randomized to a home or clinic arm. Home participants received a mailed anal HPV self-sampling kit. Clinic participants attended a clinic appointment where a clinician collected an anal HPV swab. We examined acceptability (overall thoughts, comfort with method, pain, and future willingness to swab) of home versus clinic swabbing using postswab survey responses. Results: A total of 191 individuals completed swabbing and a postswab survey (home = 53.4%, clinic = 46.6%). Mean age was 47 years (range = 25-78). Reported overall thoughts about home (71.6%) and clinic (69.7%) swabbing were mostly positive (p = 0.83). Overall thoughts about the home kit did not differ by participant characteristics, but overall thoughts about clinician swabbing differed by race (p = 0.04) and HIV status (p = 0.002). Nearly all participants (98.4%) reported they were comfortable receiving the kit or getting the swabbing in the clinic, reported little or no pain (98.4%), and reported willingness to undergo swabbing in the future (97.9%). After swabbing, clinic participants reported greater trust that swabbing can give accurate information about anal cancer risk (89.9%) than home participants (69.6%) (p < 0.001), and that swabbing will help them avoid anal cancer (clinic = 79.8%, home = 59.8%) (p = 0.01). Conclusion: Anal swabbing acceptability was high and did not differ between home and clinic. Participants reported high confidence and knowledge using the mailed anal self-sampling kit. Clinical Trial Registration number is NCT03489707.

Impact of screening programme to prevent anal cancer in high-risk patients with HIV.

INTRODUCTION: We assessed the impact of a nationwide screening programme to reduce the risk of anal cancer in a large cohort of high-risk patients with HIV. METHODS: From a large database from one referral centre, all high-risk patients with HIV (men who have sex with men, history of anal or genital warts, or previous cervix human papillomavirus-related lesions) who were eligible to enter the French anal cancer screening programme (2011-2020) were retrospectively included. Adherence to the screening programme was defined as no interval >18 months between two visits. Standardized management included perianal visualization and standard anoscopy with biopsies of macroscopic abnormalities. RESULTS: Overall, 700 patients with HIV were included (median follow-up 8.4 years [interquartile range 4.3-9.2] and 1491.6 patient-years), and 336 had one or more proctology visit. A total of 13 patients were diagnosed with anal squamous cell carcinomas. The risk of anal cancer was higher with anal intra-epithelial neoplasia grade 3 (AIN3; hazard ratio [HR] 44.5 [95% confidence interval {CI} 11.2-176.6], p < 0.001), AIN2 (HR 11.9 [95% CI 2.1-66.9], p = 0.005), or high-grade dysplasia (HR 23.4 [95% CI 7.9-69.1], p < 0.001) than with low-grade dysplasia or no lesion. Among the patients who were strictly adherent to the screening programme (4.6% [32/700]), we did not report any AIN or anal cancer, but we also did not observe any significant reduction in the risk of anal cancer (p = 0.51), AIN3 (p = 0.28), high-grade dysplasia (p = 0.19), or any AIN lesions (p = 0.10) compared with non-adherent patients. In contrast, screened patients were more likely to be diagnosed with anal warts (HR 3.71 [95% CI 2.14-6.42], p < 0.001). CONCLUSION: Macroscopic high-grade dysplasia lesions are associated with a higher risk of developing anal cancer. Despite finding no cases of cancer during the screening programme, we also did not demonstrate a clear benefit from our screening programme for the prevention of anal cancer in high-risk patients with HIV.

Knowledge and Perceived Emotions Regarding an Anal Cancer Preventive Program in People Diagnosed With HIV: A Qualitative Study.

BACKGROUND: To the best of our knowledge, no studies have yet examined the emotional repercussions of the care processes among people infected with the human immunodeficiency virus who participate in preventive anal cancer screening programs. OBJECTIVE: This study aimed to explore the knowledge, emotions, sexuality, barriers, and facilitators perceived by this patient group during the process of anal cancer screening and diagnosis. METHODS: Detailed, semistructured, qualitative interviews were completed with 17 men and 3 women to explore their knowledge, experiences, and emotions regarding the screening process. Purposive sampling was conducted on the basis of age, gender, and type of lesion diagnosed in the anal biopsy. RESULTS: Four major themes were identified: 1) knowledge of the disease and its treatment, 2) emotions perceived by the patients, 3) the influence of screening on sexual practices, and 4) facilitators and obstacles during the care provision process. Patients reported appropriate knowledge of anal cancer and human papillomavirus. Predominant emotions were worry and fear with avoidance as one of the coping strategies. CONCLUSION: These results suggest that communication of information and clinical results can be improved. IMPLICATION FOR PRACTICE: Understanding the facilitators and barriers to the program will allow the integration of interventions designed to improve healthcare provision into direct care.

Future Directions for Research on Anal Precancerous Lesion Treatment.

ABSTRACT: The benefit of treating anal precancerous lesions to reduce anal cancer progression was recently shown in people living with HIV. This will certainly impact the future development of recommendations on anal cancer prevention by including anal precancerous lesions screening and treatment for people living with HIV. However, by bringing this topic to the spotlight, it has also uncovered data that are still missing in this field and that need to be addressed by research.This article will discuss the many unanswered questions about treatment of anal precancerous lesions and future directions for research.

Psychometric Validation of the Patient Anal Cancer Knowledge Scale (PACKS) in a Cohort of Black and Hispanic/Latino Sexual and Gender Diverse Young Adults.

Lack of anal cancer information in priority populations is a major barrier to the uptake and utilization of prevention services. A validated measure of anal cancer knowledge is needed to inform patient education and shared clinical decision-making for anal cancer prevention. The purpose of this study was to validate the Patient Anal Cancer Knowledge Scale (PACKS) in a sample of GBM, namely Black and Hispanic gay, bisexual, and other men who have sex with men (GBM) and gender expansive young adults (aged 18-30 years) living in the USA (N=188). Anal cancer knowledge was hypothesized as a 3-factor scale representing (1) risk and primary prevention (9 items), (2) symptoms (5 items), and (3) screening (3 items). Confirmatory factor analysis, internal consistency, and criterion validity were assessed. The 3-factor model demonstrated adequate fit (RMSEA=0.02; CFI=0.99). All items loaded on their respective factors (p<0.01). Scale scores indicated low to moderate anal cancer knowledge and acceptable reliability: factor 1 (M=3.5; SD=2.3; range: 0-9; α=.71), factor 2 (M=2.9; SD=1.9; range: 0-5; α=.85), and factor 3 (M=2.0; SD=1.2; range: 0-3; α=.79). History of HPV vaccination (51.3%) was positively correlated with factors 1 and 2. The PACKS demonstrated good construct validity related to knowledge of anal cancer risk, prevention, symptoms, and screening. Limited anal cancer knowledge among Black and Hispanic GBM is a potential barrier to the uptake and utilization of prevention recommendations.

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

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

Effectiveness and cost-effectiveness of human papillomavirus vaccination strategies among men who have sex with men in China: a modeling study.

Introduction: The health and economic benefits of human papillomavirus (HPV) vaccination targeted at men who have sex with men (MSM) in developing settings have been rarely assessed. This study aimed to evaluate the effectiveness and cost-effectiveness of different HPV vaccination strategies among MSM in China. Methods: A Markov model was developed to simulate HPV transmission dynamics among a total of 30.73 million MSM in China. The corresponding natural history included 6 states: susceptible, infected with low-risk subtypes, high-risk subtypes, anogenital warts and anal cancer, and deaths from anal cancer. MSM were divided into three age groups with cut-off points of 27 and 45 years. Alternative vaccination strategies were built by allocating bivalent, quadrivalent, nine-valent, or no vaccine to each of the groups. We generated the prevented infections and deaths by vaccination compared with baseline (no vaccination) and calculated incremental cost-effectiveness ratios (ICERs) to determine the optimal strategy. Results: The model showed that in 10 years, at baseline, the existing cases of anogenital warts would reach 5,464,225 (IQR, 4,685,708-6,174,175); that of anal cancer would reach 1,922.95 (1,716.56-2,119.93), resulting in 940.55 (732.27-1,141.87) deaths. Under 50% vaccination coverage among one age group, the prevented cases of anogenital warts were maximized with quadrivalent vaccines allocated to MSM aged 27-45 years; that of anal cancer were maximized when offering nine-valent vaccines to the same group. Under 50% vaccination coverage among all groups, the lowest ICER (34,098.09 USD/QALY, 31,146.54-37,062.88) was reached when only quadrivalent vaccines were provided. Based on this strategy, when the annual vaccination rate increased by 30%, the ICER (33,521.75 USD/QALY, 31,040.73-36,013.92) would fall below three times China's per capita GDP. When the vaccine price decreased by 60%, the ICER was reduced to 7,344.44 USD/QALY (4,392.89-10,309.23), indicating good cost-effectiveness taking China's per capita GDP as a threshold. Conclusions: HPV vaccination can effectively reduce the prevalence and mortality of related diseases among MSM in China, especially quadrivalent vaccines for anogenital warts and nine-valent vaccines for anal cancer. MSM aged 27-45 years were the optimal group for vaccination. Annual vaccination and appropriate adjustment of vaccine price are necessary to further improve the cost-effectiveness.

Anal Cancer and Anal Cancer Screening.

This chapter provides an overview of anal cancer and contemporary approaches for anal precancer detection, beginning with a discussion of the biology and natural history of anal squamous cell carcinoma, the predominant human papillomavirus -associated histologic subtype of anal cancer. This section is followed by a description of the epidemiology of anal cancer, including trends in incidence and mortality, a discussion of populations with elevated risk for anal cancer and an overview of associated risk factors. The remainder of the chapter provides the most up-to-date evidence on tools and approaches for anal cancer prevention, screening, and early detection; including, the role of human papillomavirus vaccination for primary prevention; anal cytology, high resolution anoscopy and novel biomarkers for secondary prevention; and digital anal-rectal examination for early detection.

Home-based self-sampling vs clinician sampling for anal precancer screening: The Prevent Anal Cancer Self-Swab Study.

Sexual minority men are at increased risk for anal squamous cell carcinoma. Our objective was to compare screening engagement among individuals randomized to self-collect an anal canal specimen at home or to attend a clinic appointment. Specimen adequacy was then assessed for human papillomavirus (HPV) DNA genotyping. A randomized trial recruited cisgendered sexual minority men and transgender people in the community and assigned them to use a home-based self-collection swabbing kit or attend a clinic-based swabbing. Swabs were sent for HPV genotyping. The proportions of participants completing screening in each study arm and the adequacy of their specimens for HPV genotyping were assessed. Relative risks were estimated for factors associated with screening. A total of 240 individuals were randomized. Age (median, 46 years) and HIV status (27.1% living with HIV) did not differ by study arm. A total of 89.2% and 74.2% of home-arm and clinic-arm individuals returned the swab, respectively (P = .003), difference between groups, 15.0% (95% CI 5.4%-24.6%). Among black individuals, 96.2% and 63.2% in the home and clinic arms screened (P = .006). Among individuals with HIV, 89.5% and 51.9% in the home and clinic arms screened (P < .001). Self-collected swabs and clinician-collected swabs were comparable in adequacy for HPV genotyping (96.3% and 93.3%, respectively). People at highest risk for anal cancer may be more likely to screen if they are able to self-collect swabs at home rather than attend a clinic.

Integration of human papillomavirus associated anal cancer screening into HIV care and treatment program in Pakistan: perceptions of policymakers, managers, and care providers.

BACKGROUND: The incidence of anal cancer, largely associated with anal human papillomavirus (HPV) infection, is increasing among men who have sex with men (MSM), and transgender women living with or without HIV. Screening for anal cancer to detect anal precancerous lesions in high-risk groups is an important opportunity for prevention but still lacking in many low-and-middle-income countries. The aim of this study was to explore the readiness of Pakistan's healthcare system to integrate anal cancer and HPV screening into a national HIV program, as perceived by policymakers, health managers, and healthcare providers. DESIGN: This qualitative study using key-informant interviews with participants influence in policy making, implementation and advocacy from public and private sector were conducted between March 2021 to August 2021 in Karachi Pakistan. METHODS: Key informants were purposely selected from different domains of the healthcare system responsible for the target group of interest, MSM and transgender-women in general and people living with HIV in particular. A total of 18 key informants, at different levels of seniority were recruited from governmental and non-governmental organizations, high-level infectious disease healthcare managers, and United Nations Program representatives. Qualitative content analysis was used to identify the manifest and latent themes, based on socioecological framework. RESULTS: The results were grouped into five major themes; (1) The policy context and priorities, (2) Health systems factors, (3) Community environment, (4) Healthcare setting & providers and (5) Individual-level obstacles. The policy actors expressed their concerns about their limited voice in country's health and health related priority setting. Informants reported a lack of political will and suggested that government should bring a change in the paradigm of healthcare service delivery from reactive to proactive approach. Although, participants unanimously favored integration of HPV preventive services into existing HIV program, they also identified several service delivery barriers including trained workforce shortage, limited capacity of information technology, lack of supplies needed for screening, lack of financing, and lack of services that could meet key-populations needs. Participants also predicted other implementation challenges such as stigma, social victimization, and systemic discrimination against at-risk groups at healthcare facilities. CONCLUSION: Although policy makers and health providers in Pakistan saw a clear need to scale-up and integrate anal cancer screening for key populations, the feasibility of this is dependent on political will, financing, anti-stigma and discrimination interventions and health system efficiency.

Impact of Human Papillomavirus Vaccine Against Anal Human Papillomavirus Infection, Anal Intraepithelial Neoplasia, and Recurrence of Anal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis.

BACKGROUND: We sought to summarize human papillomavirus (HPV) vaccine efficacy/effectiveness (VE) against anal HPV infection and anal intraepithelial neoplasia (AIN). METHODS: We performed literature review and meta-analysis to estimate VE, stratified by age and analytic population (per-protocol efficacy [PPE] or intention-to-treat [ITT] population in clinical trials, or all participants in real-world studies). RESULTS: We identified 6 clinical trials and 8 real-world studies. In participants vaccinated at age ≤26 years (mainly human immunodeficiency virus [HIV]-negative individuals), significant VE against incident/prevalent anal HPV infection was reported in clinical trials, with a higher estimate in PPE (2 studies with 2390 participants; VE, 84% [95% confidence interval (CI), 77%-90%]; I2 = 0%) than ITT (2 studies with 4885 participants; 55%, 39%-67%; I2 = 46%) populations or in real-world studies (4 studies with 2375 participants; 77%, 40%-91%; I2 = 81%). HPV vaccination at age ≤26 years was associated with significant VE in preventing persistent anal HPV infection and AIN. No significant VE against anal HPV infection or AIN was found in persons vaccinated at age >26 years (mainly people living with HIV). CONCLUSIONS: There is strong evidence for high VE against anal HPV infection and AIN in HIV-negative individuals vaccinated at age ≤26 years. However, the lower impact in ITT than in PPE populations and the lack of significant effect in people living with HIV aged >26 years indicates that vaccines have the higher impact in populations with less sexual exposure to anal HPV.