Prevalence and incidence of anal high-grade squamous intraepithelial lesions in a cohort of cisgender men and transgender women who have sex with men diagnosed and treated during acute HIV acquisition in Bangkok, Thailand.

INTRODUCTION: Men who have sex with men (MSM), especially those living with HIV, are at an increased risk of anal cancer. The prevalence and incidence of its precursor, anal high-grade squamous intraepithelial lesions (HSILs), among MSM who started antiretroviral therapy during acute HIV acquisition are yet to be explored. METHODS: Participants in an acute HIV acquisition cohort in Bangkok, Thailand, who agreed to take part in this study, were enrolled. All participants were diagnosed and started antiretroviral therapy during acute HIV acquisition. Human papillomavirus (HPV) genotyping and high-resolution anoscopy, followed by anal biopsy as indicated, were done at baseline and 6-monthly visits. RESULTS: A total of 89 MSM and four transgender women were included in the analyses. Median age at enrolment was 26 years. Baseline prevalence of histologic anal HSIL was 11.8%. With a total of 147.0 person-years of follow-up, the incidence of initial histologic anal HSIL was 19.7 per 100 person-years. Factors associated with incident anal HSIL were anal HPV 16 (adjusted hazards ratio [aHR] 4.33, 95% CI 1.03-18.18), anal HPV 18/45 (aHR 6.82, 95% CI 1.57-29.51), other anal high-risk HPV (aHR 4.23, 95% CI 1.27-14.14), syphilis infection (aHR 4.67, 95% CI 1.10-19.90) and CD4 count <350 cells/mm3 (aHR 3.09, 95% CI 1.28-7.48). CONCLUSIONS: With antiretroviral therapy initiation during acute HIV acquisition, we found the prevalence of anal HSIL among cisgender men and transgender women who have sex with men to be similar to those without HIV. Subsequent anal HSIL incidence, although lower than that of those with chronic HIV acquisition, was still higher than that of those without HIV. Screening for and management of anal HSIL should be a crucial part of long-term HIV care for all MSM.

Antibodies against high-risk human papillomavirus proteins as markers for noncervical HPV-related cancers in a Black South African population, according to HIV status.

Human papillomavirus (HPV) proteins may elicit antibody responses in the process toward HPV-related malignancy. However, HPV seroepidemiology in noncervical HPV-related cancers remains poorly understood, particularly in populations with a high prevalence of human immunodeficiency virus (HIV). Using a glutathione S-transferase-based multiplex serology assay, antibodies against E6, E7 and L1 proteins of HPV16 and HPV18 were measured in sera of 535 cases of noncervical HPV-related cancers (anal (n = 104), vulval (n = 211), vaginal (n = 49), penile (n = 37) and oropharyngeal (n = 134)) and 6651 non-infection-related cancer controls, from the Johannesburg Cancer Study that recruited Black South African with newly diagnosed cancer between 1995 and 2016. Logistic and Poisson regression models were used to calculate adjusted odds ratios (aOR) and prevalence ratios (aPR) and 95% confidence intervals (CI) in cases versus controls. HPV16 E6 was more strongly associated with noncervical HPV-related cancers than HPV16 L1 or E7, or HPV18 proteins: anal (females (HPV16 E6 aOR = 11.50;95%CI:6.0-22.2), males (aOR = 10.12;95%CI:4.9-20.8), vulval (aOR = 11.69;95%CI:7.9-17.2), vaginal (aOR = 10.26;95%CI:5.0-21), penile (aOR = 18.95;95%CI:8.9-40), and oropharyngeal (females (aOR = 8.95;95%CI:2.9-27.5), males (aOR = 3.49;95%CI:1.8-7.0)) cancers. HPV16-E6 seropositivity ranged from 24.0% to 35.1% in anal, vulval, vaginal and penile cancer but was significantly lower (11.2%) in oropharyngeal cancer. After adjustment for HIV, prevalence of which increased from 22.2% in 1995-2005 to 54.1% in 2010-2016, HPV16 E6 seropositivity increased by period of diagnosis (aPR for 2010-2016 vs. 1995-2006 = 1.84;95%CI:1.1-3.0). Assuming HPV16 E6 seroprevalence reflects HPV attributable fraction, the proportion of certain noncervical-HPV-related cancers caused by HPV is increasing over time in South Africa. This is expected to be driven by the increasing influence of HIV.

Hospitalization burden associated with anus and penis neoplasm in Spain (2016-2020).

In 2020, there were approximately 50,865 anal cancer cases and 36,068 penile cancer cases worldwide. HPV is considered the main causal agent for the development of anal cancer and one of the causal agents responsible for the development of penile cancer. The aim of this epidemiological, descriptive, retrospective study was to describe the burden of hospitalization associated with anal neoplasms in men and women and with penis neoplasms in men in Spain from 2016 to 2020. The National Hospital Data Surveillance System of the Ministry of Health, Conjunto Mínimo Básico de Datos, provided the discharge information used in this observational retrospective analysis. A total of 3,542 hospitalizations due to anal cancer and 4,270 hospitalizations due to penile cancer were found; For anal cancer, 57.4% of the hospitalizations occurred in men, and these hospitalizations were also associated with significantly younger mean age, longer hospital stays and greater costs than those in women. HIV was diagnosed in 11.19% of the patients with anal cancer and 1.74% of the patients with penile cancer. The hospitalization rate was 2.07 for men and 1.45 for women per 100,000 in anal cancer and of 4.38 per 100,000 men in penile cancer. The mortality rate was 0.21 for men and 0.12 for women per 100,000 in anal cancer and 0.31 per 100.000 men in penile cancer and the case-fatality rate was 10.07% in men and 8,26% in women for anal cancer and 7.04% in penile cancer. HIV diagnosis significantly increased the cost of hospitalization. For all the studied diagnoses, the median length of hospital stays and hospitalization cost increased with age. Our study offers relevant data on the burden of hospitalization for anal and penile cancer in Spain. This information can be useful for future assessment on the impact of preventive measures, such as screening or vaccination in Spain.

Assessing the Potential of HPV16 E6 Seroprevalence as a Biomarker for Anal Dysplasia and Cancer Screening-A Systematic Review and Meta-Analysis.

Elevated rates of human papillomavirus (HPV)-related anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer (AC) in populations like men who have sex with men (MSM) living with HIV underscore the need for effective screening. While high-resolution anoscopy-guided biopsy is the gold standard, limited provider availability poses a challenge. This has spurred interest in identifying biomarkers for improved AC prevention. Antibodies against HPV16 oncoprotein E6, known as markers for cervical and oropharyngeal cancers, are the focus of the current study. The systematic review and meta-analysis included six studies meeting inclusion criteria, assessing HPV16 E6 seroprevalence in individuals with anal HSIL or AC. A two-step meta-analysis estimated pooled odds ratios and 95% confidence intervals (CI) for HPV16 E6 seroprevalence and HSIL or AC. Pooled prevalence, sensitivity, specificity, and diagnostic odds ratios were also calculated. This meta-analysis revealed a 3.6-fold increased risk of HSIL for HPV16 E6 seropositive individuals, escalating to a 26.1-fold risk increase for AC. Pooled specificity and sensitivity indicated a high specificity (0.99; 95%CI: 0.99, 0.99) but lower sensitivity (0.19; 95%CI: 0.10, 0.34) for HPV16 E6 serostatus as an AC biomarker. In conclusion, while HPV16 E6 seroprevalence demonstrates specificity as a potential biomarker for HPV-related AC, its utility as a standalone screening tool may be limited. Instead, it could serve effectively as a confirmation test, particularly in high-risk populations, alongside other diagnostic methods. Further research is imperative to explore HPV16 E6 seroconversion dynamics and alternative screening algorithms.

The risk of vaginal, vulvar and anal precancer and cancer according to high-risk HPV status in cervical cytology samples.

High-risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five-year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV-positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV-negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV-positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non-cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow-up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high-risk groups and acceptable risk thresholds.

Sexual risk characteristics, social vulnerability, and anal cancer screening uptake among men living with HIV in the deep south.

ABSTRACTWithout standard guidelines, there is a critical need to examine anal cancer screening uptake in the South which has the highest HIV incidence in the U.S. We identified factors associated with screening among men living with HIV (MLHIV) at a large academic HIV outpatient clinic in Alabama. Relationships between sociodemographic, clinical, sexual risk characteristics and screening were examined using T-tests, Fisher's exact, Chi-square, and logistic regression analyses. Unadjusted and adjusted odds ratios (AOR) were computed to estimate the odds of screening. Among 1,114 men, 52% had received annual anal cytology (pap) screening. Men who were screened were more likely to have multiple sexual partners compared to men who were not screened (22.8% vs. 14.8%, p = 0.002). Among men with one partner, the youngest were almost five times more likely to be screened compared to middle-aged men (AOR = 4.93, 95% CI: 2.34-10.39). Heterosexual men had lower odds and men who reported unprotected anal sex had higher odds of screening. Our findings suggest a racial disparity, with older black MLHIV being the least likely to be screened. In the South, MLHIV who are older, black, heterosexual, or live in high social vulnerability counties may be less likely to receive annual anal cancer screening.

Unraveling Emerging Anal Cancer Clinical Biomarkers from Current Immuno-Oncogenomics Advances.

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk human papillomavirus (HPV) and is currently one of the fastest-growing causes of cancer incidence and mortality in developed countries. Although next-generation sequencing technologies (NGS) have revolutionized cancer and immuno-genomic research in various tumor types, a limited amount of clinical research has been developed to investigate the expression and the functional characterization of genomic data in ASCC. Herein, we comprehensively assess recent advancements in "omics" research, including a systematic analysis of genome-based studies, aiming to identify the most relevant ASCC cancer driver gene expressions and their associated signaling pathways. We also highlight the most significant biomarkers associated with anal cancer progression, gene expression of potential diagnostic biomarkers, expression of therapeutic drug targets, and emerging treatment opportunities. This review stresses the urgent need for developing target-specific therapies in ASCC. By illuminating the molecular characteristics and drug-target expression in ASCC, this study aims to provide insights for the development of precision medicine in anal cancer.

Survival by sex and HIV status in patients with anal cancer in the USA between 2001 and 2019: a retrospective cohort study.

BACKGROUND: The risk of anal cancer is increased among people with HIV, particularly men who have sex with men. Estimating survival by HIV status and sex and identifying groups at high risk is crucial for documenting prognostic differences between populations. We aimed to compare all-cause and anal cancer-specific survival in patients with anal cancer with and without HIV, stratified by sex, and to identify predictors of survival, stratified by HIV status. METHODS: In this retrospective cohort study, we used data from the HIV/AIDS Cancer Match Study of 13 population-based HIV and cancer registries throughout the USA. We included individuals aged 20-79 years diagnosed with invasive anal cancer between 2001 and 2019. To estimate associations between HIV status and both all-cause and anal cancer-specific mortality overall, we used Cox proportional hazards models, adjusting for year of and age at diagnosis, sex, race and ethnicity, histology, cancer stage, region, and treatment. We also calculated sex-specific adjusted hazard ratios (HRs). By HIV status, we identified characteristics associated with mortality. Models among people with HIV were further adjusted for AIDS status and HIV transmission risk group. FINDINGS: Between Jan 1, 2001, and Dec 31, 2019, 1161 (43·6%) of 2662 patients with anal cancer and HIV and 7722 (35·4%) of 21 824 patients without HIV died. HIV was associated with a 1·35 times (95% CI 1·24-1·47) increase in all-cause mortality among male patients and a 2·47 times (2·10-2·90) increase among female patients. Among patients with HIV, all-cause mortality was increased among non-Hispanic Black individuals (adjusted HR 1·19, 95% CI 1·04-1·38), people with AIDS (1·36, 1·10-1·68), people who inject drugs (PWID; 1·49, 1·17-1·90), patients with adenocarcinoma (2·74, 1·82-4·13), and those with no or unknown surgery treatment (1·34, 1·18-1·53). HIV was associated with anal cancer-specific mortality among female patients only (1·52, 1·18-1·97). Among patients with HIV, anal cancer-specific mortality was increased among patients with adenocarcinoma (3·29, 1·89-5·72), those with no or unknown treatment (1·59, 1·17-2·17), and PWID (1·60, 1·05-2·44). INTERPRETATION: HIV was associated with all-cause mortality among patients with anal cancer, especially women. Anal cancer-specific mortality was elevated among female patients with HIV. As screening for anal cancer becomes more widespread, examining the effects of screening on survival by HIV status and sex is crucial. FUNDING: US National Cancer Institute Intramural Research Program.

Human papillomavirus-associated anal squamous cell carcinoma: sociodemographic, geographic, and county-level economic trends in incidence rates-United States, 2001-2019.

BACKGROUND: Incidence of anal squamous cell carcinoma is increasing, but vaccination against human papillomavirus (HPV) and removal of precancerous anal lesions could prevent new cases. The overall HPV-associated cancer incidence is reported to be higher in rural populations and in counties with lower economic status. We assessed these differences specifically for HPV-associated anal squamous cell carcinoma and described the geographic, county-level economic, and sociodemographic variations in incidence rates and trends. METHODS: We analyzed data from the US Cancer Statistics to assess age-standardized incidence rates of HPV-associated squamous cell carcinomas among adults aged 18 years and older from 2001 to 2019. We calculated rate ratios and 95% confidence intervals to examine differences in incidence rates. We also quantified changes in incidence rates over time using joinpoint regression. RESULTS: From 2001 to 2019, 72 421 new cases of HPV-associated anal squamous cell carcinoma were diagnosed among women (2.8 per 100 000) and 37 147 among men (1.7 per 100 000). Age-standardized incidence rates were higher in the South compared with other census regions and in counties ranked in the bottom 25% and 25%-75% economically than in the top 25%. The overall incidence rate increased in women but remained stable in men during 2009-2019. Incidence rates increased in adults aged 50 years and older but decreased among those aged 40-44 years from 2001 to 2019 in women and from 2007 to 2019 in men. CONCLUSIONS: There were inequities in HPV-associated anal squamous cell carcinoma incidence by geographic and county-level economic characteristics. Failure to improve vaccine and treatment equity may widen existing disparities.

Severe anal intraepithelial neoplasia trends and subsequent invasive anal cancer in the United States.

BACKGROUND: Anal intraepithelial neoplasia grade III is a precursor to squamous cell carcinoma of the anus for which rates are nearly 20-fold higher in people with HIV than in the general population in the United States. We describe trends in anal intraepithelial neoplasia grade III diagnosis and risk of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III by HIV status and sex. METHODS: We used data from a population-based linkage between cancer and HIV registries in 11 US states; Puerto Rico; and Washington, DC, during 1996-2019. We identified all individuals with a diagnosis of anal intraepithelial neoplasia grade III and determined their HIV status. We estimated the average annual percentage change of anal intraepithelial neoplasia grade III using Poisson regression stratified by HIV status and sex. We estimated the 5-year cumulative incidence of squamous cell carcinoma of the anus following an anal intraepithelial neoplasia grade III diagnosis stratified by sex, HIV status, and prior AIDS diagnosis. RESULTS: Among people with HIV, average annual percentage changes for anal intraepithelial neoplasia grade III were 15% (95% confidence interval [CI] = 12% to 17%) per year among females and 12% (95% CI = 11% to 14%) among males. Average annual percentage changes for those without HIV were 8% (95% CI = 7% to 8%) for females and 8% (95% CI = 6% to 9%) for males. Among people with HIV, a prior AIDS diagnosis was associated with a 2.7-fold (95% CI = 2.23 to 3.40) and 1.9-fold (95% CI = 1.72 to 2.02) increased risk of anal intraepithelial neoplasia grade III diagnosis for females and males, respectively. Five-year cumulative incidence of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III for people with HIV with a prior AIDS diagnosis were 3.4% and 3.7% for females and males, respectively. CONCLUSIONS: Rates of anal intraepithelial neoplasia grade III diagnoses have increased since 1996, particularly for people with HIV, likely influenced by increased screening. A prior AIDS diagnosis was strongly associated with risk of anal intraepithelial neoplasia grade III diagnosis.

Autoimmune disease and the risk of anal cancer in the US population aged 66 years and over.

BACKGROUND: In the United States, anal squamous cell carcinoma rates have increased rapidly, particularly among women 50 or older than 66 years of age. As immunosuppression is associated with increased risk, autoimmune conditions may be associated with greater risk of anal squamous cell carcinoma. METHODS: We conducted a population-based, case-control study using Surveillance, Epidemiology, and End Results-Medicare data (2000-2017). Anal squamous cell carcinoma cases (n = 4505) were matched to 200 000 cancer-free controls. Using multivariable logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between 47 autoimmune conditions diagnosed before selection, identified using Medicare claims, and anal squamous cell carcinoma. The Bonferroni threshold was used to correct for multiple comparisons. Population attributable fractions were calculated for conditions nominally associated with anal squamous cell carcinoma. RESULTS: In total, 18% of anal squamous cell carcinoma cases and 15% of cancer-free controls had a diagnosed autoimmune condition. Any autoimmune condition was associated with an increased risk of anal squamous cell carcinoma (OR = 1.11, 95% CI = 1.02 to 1.21; population attributable fraction = 1.8%). Anal squamous cell carcinoma was associated with systemic lupus erythematosus (OR = 1.79, 95% CI = 1.32 to 2.42; population attributable fraction = 0.4%) and nominally associated (P < .05) with sarcoidosis (OR = 2.09, 95% CI = 1.30 to 3.37; population-attributable fraction = 0.2%) and psoriasis (OR = 1.28, 95% CI = 1.06 to 1.56; population attributable fraction = 0.5%). Stratified by sex, only women showed statistically significant associations for systemic lupus erythematosus (OR = 1.97, 95% CI = 1.46 to 2.68). Statistically significant interaction was observed by sex for psoriasis (men vs women: OR = 1.68 [95% CI = 1.03 to 4.28] vs OR = 1.12 [95% CI = 0.88 to 1.43]) and polymyalgia rheumatica (OR = 0.33 [95% CI = 0.12 to 0.89] vs OR = 0.99 [95% CI = 0.75 to 1.30]). CONCLUSION: Systemic lupus erythematosus, sarcoidosis, and psoriasis were associated with a moderately increased risk of anal squamous cell carcinoma. Given these conditions' rarity and moderate associations with anal squamous cell carcinoma, autoimmune diseases cannot explain the rising trend in this disease.

Monitoring Patients With Inflammatory Bowel Disease at High Risk of Anal Cancer.

Anal cancer is a rare but deadly disease that disproportionately affects patients with inflammatory bowel disease (IBD). Rates of adenocarcinoma and human papillomavirus-related squamous cell carcinoma have been consistently demonstrated to be higher in patients with ulcerative colitis and Crohn's disease. Despite this increased risk, uniform screening, diagnosis, and treatment algorithms are lacking. This review describes the most recent literature surrounding anal cancer in the IBD population as well as the unique challenges inherent in diagnosing and treating this population. We conclude by proposing a new screening motif based off literature review and multidisciplinary clinical experience that aims to increase early detection of anal cancers in the IBD population.

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.

Global trends in anal cancer incidence and mortality.

OBJECTIVE: Anal cancer is a rare disease, affecting more frequently women than men, mainly related to human papillomavirus infection (HPV). Rising incidence and mortality have been reported over the past four decades in different countries. METHODS: To provide an up-to-date overview of recent trends in mortality from anal cancer, we analysed death certification data provided by the WHO in selected countries worldwide over the period from 1994 to 2020. We also analysed incidence derived from Cancer Incidence in Five Continents from 1990 to 2012 for all histologies as well as for anal squamous cell carcinoma (SCC). RESULTS: The highest age-standardised mortality rates around 2020 were registered in Central and Eastern Europe, such as Slovakia (0.9/100 000 men and 0.40/100 000 women), in the UK (0.24/100 000 men and 0.35/100 000 women), and Denmark (0.33/100 000 for both sexes), while the lowest ones were in the Philippines, Mexico, and Japan, with rates below 0.10/100 000 in both sexes. Upwards trends in mortality were reported in most countries for both sexes. Similarly, incidence patterns were upward or stable in most countries considered for both sexes. In 2008-2012, Germany showed the highest incidence rates (1.65/100 000 men and 2.16/100 000 women). CONCLUSION: Attention towards vaccination against HPV, increased awareness of risk factors, mainly related to sexual behaviours and advancements in early diagnosis and management are required to control anal cancer incidence and mortality.

Awareness of the causal association between human papillomavirus and anal cancer among US adults.

PURPOSE: The incidence of anal cancer is on the rise in the US, especially among high-risk groups. This study examined the prevalence and determinants of awareness of the causal relationship between HPV and anal cancer among US adults. METHODS: Study data was obtained from the 2017 to 2020 iterations of the Health Information National Trends Survey. The prevalence of awareness that HPV causes anal cancer was estimated among HINTS respondents who were aware of HPV in general. Survey weights were used to provide estimates representative of the adult US population. Multivariable logistic regressions were used to examine the associations between awareness that HPV causes anal cancer and cancer-related behaviors/perceptions and sociodemographic characteristics of respondents. RESULTS: Two thousand six hundred and eighty four (27.2%) of the study population were aware that HPV caused anal cancer. Those of gay sexual orientation were more aware than heterosexuals [OR 2.27; 95% CI (1.24, 4.14)]. Compared to respondents with a high school diploma or less, individuals with some college education [OR 1.38; 95% CI (1.03, 1.85)] and those with at least a college degree [OR 1.52; 95% CI (1.17, 1.98)] were more likely to be aware. Participants who had positive cancer information seeking behavior were more aware of the HPV-anal cancer link compared to those who did not [OR 1.57; 95% CI (1.30, 1.89)]. CONCLUSION: Population-level awareness that HPV causes anal cancer remains critically low in the US. Sexual orientation, level of education and cancer information seeking behavior are associated with increased awareness of the causal relationship between HPV and anal cancer. Efforts should be directed toward addressing the awareness gap among individuals with lower education levels and promoting curiosity-driven information seeking behaviors.

Anal cancer screening results from 18-to-34-year-old men who have sex with men living with HIV.

Men who have sex with men living with HIV (MSM LWH) are at highest risk for human papillomavirus (HPV)-associated anal cancer. There is no consensus on the optimal screening initiation age. This study aimed to assess the prevalence and severity of anal HPV disease among MSM LWH under the age of 35, which is a currently proposed screening age threshold. Between 2014 and 2020, 1255 18-to-34-year-old MSM LWH underwent anal cytology screening. 916 were co-tested for high-risk HPV (HR-HPV). 467 underwent high-resolution anoscopy (HRA) and biopsy. Cancer registry data were queried. Predictors of abnormal cytology (ie, ≥ASCUS) and histological high-grade squamous intraepithelial lesions (HSIL) were evaluated using unadjusted logistic regression models. Median age was 28 years (range, 18-34). 19% received at least one dose of HPV vaccine. Abnormal cytology rate was 65%. HR-HPV and HPV16 prevalence were 87% and 30%. Biopsy results were benign (10%), LSIL (43%) and HSIL (47%). No cases of prevalent or incident anal cancers were detected. Findings were similar between age subgroups (18-24, 25-29 and 30-34) except for a higher prevalence of AIN 3 in the 30-34 group (19%). Abnormal cytology was significantly associated with HR-HPV infection. Histological HSIL was associated with HR-HPV infection and cytological LSIL or worse. The absence of anal cancer in a large cohort of MSM LWH under the age of 35, despite high prevalence of anal HR-HPV infection and precancer, supports an age-based anal cancer screening strategy for MSM LWH.

Trends in epidemiology and primary treatment of anal squamous cell carcinoma in the Netherlands (1990-2021).

A rapid increase in the incidence of anal squamous cell carcinoma (SCC) was reported in several countries over the past decades. This study assessed trends in epidemiology and primary treatment over a 32-year period (1990-2021) using the Netherlands Cancer Registry. The study population included 4273 patients, 44.2% male and 55.8% female (median age 63 years). The age-standardised incidence rate (European Standardised Rate, ESR) increased from 0.5 to 1.6 per 100,000, which entailed an average annual percentage change (AAPC) of 5.0% (95% confidence interval [CI]: 4.5%-5.8%). While incidence among females increased continuously over the total period (AAPC 4.9%; 95%CI: 4.4%-5.6%), to 1.8 per 100,000 ESR in 2021, incidence among males increased until 2016 (annual percentage change [APC] of 6.3%; 95%CI: 5.6%-10.7%), after which it seemed to stabilise (APC -2.1%; 95%CI: -16.8%-4.5%). Significant trends were also observed in distribution of age, tumour stage and primary treatment modalities. Five-year relative survival (RS) was estimated using the Pohar-Perme estimator, and this improved from 56.1% in 1990-1997 (95%CI: 49.3%-62.4%) to 67.9% in 2014-2021 (95%CI: 64.7%-70.9%), but remained poor for stage IV disease. Evaluation through a multivariable Poisson regression model demonstrated diagnosis in the most recent period to be independently associated with better RS, in addition to female sex, younger age, early disease stage and any treatment. In conclusion, the rising incidence of anal SCC seems to decline in males, but not in females, and advances in diagnostics and therapeutic management have likely contributed to improved prognosis.

A comprehensive review of anal cancer-with a special focus on anal cytology.

The diagnosis of anal cancer is relatively uncommon, but its incidence has been steadily increasing in high-risk populations. In the 2001 Bethesda System for Reporting Cervical Cytology, anal cytology was introduced as a component. Since then, it has been recognized as a potential tool for screening anal cancer, often in conjunction with high-resolution anoscopy. There are notable similarities between anal cancer and cervical cancer, including the causative role of human papillomavirus. However, there are also significant differences, particularly in terms of disease prevalence. Anal cytology may be used as a primary screening test, and in the event of abnormalities, patients are subsequently directed for high-resolution anoscopy. However, the best approach for anal cancer screening is yet to be determined and uniformly implemented. This comprehensive review article provides an in-depth analysis of the epidemiology and incidence of anal precursor and malignant lesions. It explores the various methods of sample procurement, preparation, interpretation (including sensitivity and specificity), and reporting terminology in anal cytology. The article also addresses the significance of concurrent high-risk human papillomavirus screening in anal cytology and its role in screening programs. Furthermore, it discusses the follow-up, prevention, and subsequent management strategies for anal cancers. By synthesizing current knowledge in these areas, this review aims to provide a comprehensive understanding of anal cytology and its implications in the early detection, prevention, and management of anal neoplasia and cancer.

Anal Dysplasia Screening in People Living with HIV: Long-Term Follow-Up in a Large Cohort from Northwest Spain.

Anal squamous cell carcinoma (SCC) is not a common disease in the general population, although its incidence is higher in people living with human immunodeficiency virus (PLWH). Anal SCC is caused by human papillomavirus (HPV) infection and arises from premalignant lesions termed squamous intraepithelial lesions (SILs). SIL surveillance programs are based on the early detection and treatment of SILs, especially those with a higher risk of transforming into cancer. An anal surveillance program has been under development in our institution since 2011. In this context, we performed a retrospective cohort study at the anal dysplasia unit of Álvaro-Cunqueiro Hospital (Spain). Epidemiological and clinical data were gathered from our Infectious Diseases Sample Collection (an open sample cohort including PLWH) from January 2011 to January 2022. A total of 493 PLWH were considered, 122 (24.7%) of whom were diagnosed with anal dysplasia at baseline, including 2 cases of anal SCC. Briefly, most of individuals were young men (median age, 38 years old) born in Spain (76%), whose vaccination rate before their inclusion in the program was scarce (<3%). Throughout the study period, 81 (16.4%) cases were diagnosed with high-grade squamous-intraepithelial lesions (HSILs) and 3 with anal SCC. At the baseline, severe immunosuppression (i.e., nadir CD4+ lymphocyte count below 200 cell/µL), and prior diagnosis of condyloma acuminata were more frequent within the group with SILs. Conversely, the baseline CD4+ lymphocyte count was similar among both groups. HPV-16 was related to a higher risk of HSILs (odds ratio: 2.76). At the end of the follow-up, 385 PLWH had been retained in care; one patient had died of anal cancer. Anal dysplasia was common (25% of cases), especially among patients infected by HPV-16, diagnosed with condyloma acuminata, and who were severely immunosuppressed. HPV-16 was the main risk factor for the presentation of HSILs.