Australian guidelines for anal cancer screening using anal human papillomavirus testing with cytology triage in people living with HIV.

The American Society of Colon and Rectal Surgeons is dedicated to ensuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. The Clinical Practice Guidelines Committee is composed of society members who are chosen

Background Screening for the anal cancer precursor HSIL is not recommended in national guidelines. A recent Cochrane review of HSIL treatment concluded there is no evidence of efficacy. In this context, we aimed to describe the natural history of anal HSIL, and association with human papillomavirus (HPV), in a community-recruited cohort of Australian homosexual men. Methods: The SPANC study is a three-year prospective study in men aged =35 years. At each visit, men undergo an anal swab for cytology and HPV genotyping (Roche Linear Array), followed by high-resolution anoscopy-aided biopsy. Anal HSIL is defined as having either anal intraepithelial neoplasia grade 2/3 on histology and/or HSIL/ASC-H on cytology. Results: Among 342 men recruited by March 2013, median age was 49 with 29% HIV positive. At baseline, prevalence of anal HSIL was 50% and 44% in the HIV-positive and HIV-negative groups, respectively (P = 0.303). Among those without HSIL at baseline, HSIL incidence was 28/100 person-years in both the HIV-positive and HIV-negative groups (P = 0.920). Among those with HSIL at baseline, the incidence of change to non-HSIL was 41 and 43/100 person-years (P = 0.851). Men with anal HPV16 at baseline were more likely to develop incident HSIL (57 vs 23/100 person-years, P = 0.010), and less likely to change to non-HSIL (18 vs 61/100 person-years, P = 0.001). Conclusions: Anal HSIL was highly prevalent in these homosexual men. Both incidence of HSIL and change to non-HSIL were common, and were closely associated with HPV16 status. HPV16 positivity may identify men with HSIL at higher risk of anal cancer.

Anal squamous cell carcinoma is relatively rare, but its incidence and mortality have been increasing worldwide. While anal cytology is a sensitive cancer screening modality, its specificity is low, and data for concurrent high-risk human papilloma virus (HR-HPV) testing are limited. At our institution, anal cancer screening consists of combined anal cytology and high-risk human papilloma virus (HR-HPV) testing on all specimens. The aims of the study were to correlate results of atypical cytological diagnoses [atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells cannot exclude high grade squamous intraepithelial lesion (ASC-H)] with HR-HPV testing and determine if co-testing may potentially influence management. A retrospective search over 24-months was performed for anal cytology specimens with diagnoses of ASCUS and ASC-H. Corresponding HR-HPV (HPV 16/18 and Other-31/33/35/39/45/51/52/56/58/59/66/68) results were retrieved, and concordance/discordance was recorded. Cytology results were correlated with anal biopsy diagnoses, when available. A total of 139 patients, including 127 with ASCUS and 12 with ASC-H, were identified. Of the ASCUS cases, 90/127 (70.9%) had HR-HPV, and a squamous intraepithelial lesion (SIL) was evident in 20/39 (51.2%) of biopsies. All 12/12 (100%) ASC-H were associated with HR-HPV and 3/6 (50%) biopsies had a SIL. Our study supports use of concurrent cytology and HR-HPV for anal cancer screening cytology. Co-testing improves specificity of atypical cytology diagnoses and can identify patients requiring further intervention.

Genital warts are the most common sexually transmitted infection (STI) and are caused by human papillomavirus (HPV). Persistent anal infection by oncogenic genotypes of HPV is a determinant for anal cancer. Currently, anal cancer screening is not widely implemented. Our aim is to evaluate the role of perianal warts as a risk marker for anal high-risk (HR) HPV detection and anal dysplasia. In this observational, retrospective, cohort study of attendees of a STI outpatient clinic between January 2010 and June 2018, all human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) who performed anal cytology, anal HPV DNA detection and anoscopy were included. A comparison was made between patients with and without perianal warts. Primary endpoint: proportion of patients with an abnormal anal cytology. Secondary endpoints: proportion of patients with (i) anal HR-HPV detection; (ii) anal HPV 16 detection; (iii) abnormal anal biopsy; and (iv) anal high-grade squamous intraepithelial lesion (HSIL). Seventy-eight individuals were included: 39 with perianal warts and 39 without perianal warts. Subjects with perianal warts more frequently had an abnormal anal cytology (71.8% vs. 38.5%; P=0.003). This group also had a higher rate of anal HPV 16 detection (38.5% vs. 12.8%; P=0.01). No differences were detected in the proportion of patients with anal HR-HPV detection, with an abnormal anal biopsy or with anal HSIL. Perianal warts was an independent risk factor for an abnormal anal cytology (OR: 7.2) and for anal HPV 16 detection (OR: 6.7). Given the high risk of anal cancer in HIV-positive MSM, effective screening strategies are greatly needed. This study suggests that the presence of perianal warts is a suitable risk marker for anal HPV 16 detection and anal dysplasia.

The incidence of anal cancer is higher in women than men in the general population and has been increasing for several decades. Similar to cervical cancer, most anal cancers are associated with human papillomavirus (HPV), and it is believed that anal cancers are preceded by anal high-grade squamous intraepithelial lesions (HSIL). Our goals were to summarize the literature on anal cancer, HSIL, and HPV infection in women and to provide screening recommendations in women. A group of experts convened by the American Society for Colposcopy and Cervical Pathology and the International Anal Neoplasia Society reviewed the literature on anal HPV infection, anal SIL, and anal cancer in women. Anal HPV infection is common in women but is relatively transient in most. The risk of anal HSIL and cancer varies considerably by risk group, with human immunodeficiency virus-infected women and those with a history of lower genital tract neoplasia at highest risk compared with the general population. While there are no data yet to demonstrate that identification and treatment of anal HSIL leads to reduced risk of anal cancer, women in groups at the highest risk should be queried for anal cancer symptoms and required to have digital anorectal examinations to detect anal cancers. Human immunodeficiency virus-infected women and women with lower genital tract neoplasia may be considered for screening with anal cytology with triage to treatment if HSIL is diagnosed. Healthy women with no known risk factors or anal cancer symptoms do not need to be routinely screened for anal cancer or anal HSIL.

Simple SummaryHuman papillomavirus (HPV)-associated cancers, such as anal cancer, are a major risk among people living with HIV (PLWH). High-risk (HR) HPVs are the causal agent of anal precancer and cancer. However, there is a paucity of data regarding the HPV genotypes that cause especially anal cancers and pre-cancers in PLWH. In this study we characterize the specific HPV types in anal tissues, including benign, pre-cancer, and cancer samples from PLWH, and compare them to similar samples from HIV-negative individuals. The results from our study suggest that a broader range of HPV types may play a role in anal cancer in PLWH than in HIV-negative individuals. Proposed screening approaches that include HPV testing might need to differ by HIV status, with extended HPV genotyping included for PLWH.The incidence of anal cancer is increasing, especially in high-risk groups, such as PLWH. HPV 16, a high-risk (HR) HPV genotype, is the most common genotype in anal high-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) in the general population. However, few studies have described the distribution of HR HPV genotypes other than HPV 16 in the anus of PLWH. HPV genotyping was performed by DNA amplification followed by dot-blot hybridization to identify the HR and low-risk (LR) genotypes in benign anal lesions (n = 34), HSIL (n = 30), and SCC (n = 51) of PLWH and HIV-negative individuals. HPV 16 was the most prominent HR HPV identified, but it was less common in HSIL and SCC from PLWH compared with HIV-negative individuals, and other non-HPV 16 HR HPV (non-16 HR HPV) types were more prevalent in samples from PLWH. A higher proportion of clinically normal tissues from PLWH were positive for one or more HPV genotypes. Multiple HPV infection was a hallmark feature for all tissues (benign, HSIL, SCC) of PLWH. These results indicate that the development of anal screening approaches based on HPV DNA testing need to include non-16 HR HPVs along with HPV 16, especially for PLWH. Along with anal cytology, these updated screening approaches may help to identify and prevent anal disease progression in PLWH.

Women with HIV face a significantly elevated risk of developing anal cancer (AC). However, data about screening (S) implementation in clinical practice and women's acceptability are still scarce. Since October 2022 our clinic implemented anal cancer screening (ACS) using anal HPV-DNA/cytology for women with HIV. Women with at least one positive result from these tests were referred for a high-resolution anoscopy (HRA). We collected demographic and clinical data, ACS adherence rates and reasons for refusal. Multivariable analyses were conducted to identify factors associated with ACS refusal and the presence of high-risk human papilloma virus (HPV) genotypes, HSIL and AC. ACS was offered to 331 women with HIV, but 150 (45.3%) refused testing: main reasons for refusal included lack of specific concerns, no history of anal sex and a perception of not being at risk of having AC. One hundredmeightyone women underwent ACS. Cytology and HPV-DNA were positive in 54 (29.8%) and 139 (76.8%) cases. High-risk HPV genotypes were detected in 94 (67.6%) women with HIV. HSIL, LSIL and ASC-US were detected in 8 (4.4%), 43 (23.7%) and 3 (1.6%) women with HIV, respectively. Of the 135 women (93.7%) who underwent HRA, 19 (14.1%) had lesions requiring biopsies: 6 were negative, 5 were positive for dysplastic polyps, and 8 (5.5%) were diagnosed with AC. Older age, lower nadir CD4 counts, and a previous history of cervical HPV-related disease were significant risk factors for HSIL and AC. Conversely, partial or complete HPV vaccination were protective factors against high-risk HPV infection. Despite the high prevalence of anal HR-HPV genotypes and the high risk of AC among women with HIV, the uptake of ACS in our cohort was notably low. Among those who participated, a high prevalence of HPV infection and associated cytological abnormalities was observed, indicating an urgent need for increased awareness and education regarding AC in this population. The findings identify crucial risk factors, such as older age and lower CD4 counts, while also suggesting that HPV vaccination may offer protective benefits against high-risk HPV infections. These insights emphasize the importance of targeted screening programmes and interventions to improve health outcomes for women with HIV.

HIV-positive women with anal high-grade squamous intraepithelial lesions: a study of 153 cases with long-term anogenital surveillance.

Women with human immunodeficiency virus (WWH) have an elevated risk for human papillomavirus (HPV)-associated anal cancer. Primary anal cancer screening results from this population could inform practice guidelines. In total, 381 WWH with anal cytology screening, high-risk HPV (hrHPV) testing and genital (cervical or vaginal) cotesting within 6 months were identified during 2012-2019. Those with anal cytology of atypical squamous cells of undetermined significance (ASCUS) or worse underwent high-resolution anoscopy and biopsy. Independent predictors of anal hrHPV, HPV16, and histological anal high-grade squamous intraepithelial lesions (aHSIL) were identified using adjusted logistic regression models. Prevalence of anal hrHPV, HPV16, and ASCUS or worse cytology was 61%, 13%, and 68%. Histological aHSIL was detected in 42% of WWH with ASCUS or worse anal cytology. Prevalence of genital hrHPV, HPV16, and ASCUS or worse cytology was 30%, 4%, and 28%. Genital hrHPV predicted anal hrHPV (odds ratio [OR], 5.05), while genital HPV16 predicted anal HPV16 (OR, 9.52). Genital hrHPV and anal HPV16 predicted histological aHSIL (ORs, 2.78 and 10.9). Anal HPV disease was highly prevalent in this primary screening cohort of WWH. While genital screening results predicted anal disease, rates of isolated anal HPV disease were substantial, supporting universal anal cancer screening for this population.

Anal high-grade squamous intraepithelial lesion (HSIL) can be histomorphologically categorized into anal intraepithelial neoplasia (AIN) grade 2 (AIN2) and grade 3 (AIN3). Different risk factors for these two categories have been described. We investigated whether there were also differences in lesion-specific human papillomavirus (HPV) genotypes. The Study of the Prevention of Anal Cancer (SPANC) recruited 617 gay and bisexual men (GBM); 36% of participants were HIV positive. At baseline, 196 men (31.8%) had histologic HSIL lesions. Tissue was available for genotyping in 171, with a total of 239 HSIL lesions (183 AIN3 and 56 AIN2). Using laser capture microdissection, each lesion revealed a maximum of one genotype. High-risk HPV (HR-HPV) genotypes were found in 220 (92.1%) HSIL lesions, with no significant difference between AIN3 (93.4%) and AIN2 (87.5%). AIN3 lesions had significantly more HPV16 (42.1%) than AIN2 lesions (12.5%; P < 0.001) and AIN2 lesions had significantly more non-16 HR-HPV types (75.0%) than AIN3 lesions (51.4%; P = 0.002). These associations were similar for HIV-negative men with HPV16 in 51.1% AIN3 and 18.2% AIN2 (P = 0.001) and non-16 HR-HPV in 40.0% AIN3 and 75.8% AIN2 (P < 0.001). For HIV-positive men, HPV16 remained more frequently detected in AIN3 (33.3% vs. 4.4% for AIN2; P = 0.004), but there was no difference between AIN3 and AIN2 for non-16 HR-HPV (62.4% vs. 73.9%; P = 0.300). As HPV16 has the strongest link with anal cancer, the subcategorization of HSIL may enable stratification of lesions for anal cancer risk and guide anal HSIL management. Stratification of anal cancer risk by histologic HSIL grade.

Screening to prevent anal cancer: Current thinking and future directions.

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

SfondoRecently, the International Anal Neoplasia Society (IANS) has developed consensus guidelines for anal cancer (AC) prevention. IANS identified MSM living with HIV (MSM-LWH) aged ≥35 years as a priority group...

Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis

Annals for Educators - 2 January 2018.