Does use of anal cytology as a triage test improve the performance of high-risk human papillomavirus screening in gay and bisexual men for anal cancer prevention?

Anal high-risk human papillomavirus (HRHPV) testing-based anal cancer screening gay and bisexual men (GBM) is associated with high sensitivity, but low specificity. We report the potential role of triage use of anal cytology with HRHPV testing in detecting 12-month persistent anal high-grade squamous epithelial lesions (HSIL) in a cohort of GBM in Sydney, Australia. Participants were GBM from the Study of the Prevention of Anal Cancer (SPANC) who underwent annual anal HPV testing, cytology, and high-resolution anoscopy (HRA)-guided histology. The sensitivity and specificity of five screening algorithms based on HRHPV test results with triage use of anal cytology (atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells, cannot exclude HSIL (ASC-H) used as referral thresholds) were compared to these of HRHPV testing and anal cytology alone. A total of 475 men who had valid HRHPV, cytological, and histological results at both baseline and first annual follow-up visits were included, median age 49 years (inter-quartile range: 43-56) and 173 (36.4%) GBM with human immunodeficiency virus. Of all triage algorithms assessed, two had comparable sensitivity with HRHPV testing alone in detecting persistent anal HSIL, but ~20% higher specificity and 20% lower HRA referral rates. These two algorithms involved the immediate referral of those with HPV16 and for those with non-16 HRHPV either immediate or delayed (for 12 months) referral, depending on cytology result at baseline. Triage use of anal cytology in GBM testing positive for anal HRHPV increases specificity and reduces referral rates while maintaining high sensitivity in detection of HSIL.

International Anal Neoplasia Society's consensus guidelines for anal cancer screening.

The International Anal Neoplasia Society (IANS) developed consensus guidelines to inform anal cancer screening use among various high-risk groups. Anal cancer incidence estimates by age among risk groups provided the basis to identify risk thresholds to recommend screening. Guided by risk thresholds, screening initiation at age 35 years was recommended for men who have sex with men (MSM) and transgender women (TW) with HIV. For other people with HIV and MSM and TW not with HIV, screening initiation at age 45 years was recommended. For solid organ transplant recipients, screening initiation beginning from 10 years post-transplant was recommended. For persons with a history of vulvar precancer or cancer, screening initiation was recommended starting within 1 year of diagnosis of vulvar precancer or cancer. Persons aged ≥45 years with a history of cervical/vaginal HSIL or cancer, perianal warts, persistent (>1 year) cervical HPV16, or autoimmune conditions could be considered for screening with shared decision-making, provided there is adequate capacity to perform diagnostic procedures (high-resolution anoscopy [HRA]). Anal cytology, high-risk (hr) human papillomavirus (HPV) testing (including genotyping for HPV16), and hrHPV-cytology co-testing are different strategies currently used for anal cancer screening that show acceptable performance. Thresholds for referral for HRA or follow-up screening tests are delineated. These recommendations from IANS provide the basis to inform management of abnormal screening results, considering currently available screening tools. These guidelines provide a pivotal foundation to help generate consensus among providers and inform the introduction and implementation of risk-targeted screening for anal cancer prevention.

Factors Associated With Recent Decline in Anal Health Among Older Gay and Bisexual Men: A Cross-sectional Analysis.

ABSTRACT: We investigated factors associated with "worse than usual" anal health among gay and bisexual men aged ≥35 years recruited to a longitudinal study of anal human papillomavirus infection/lesions from September 2010 to August 2015.Among 616 participants (median age 49 years; 36% HIV-positive), 42 (6.8%) reported worse than usual anal health in the last 4 weeks. Associated factors included spending less time with gay friends (odds ratio [OR] = 2.25, 95% CI = 1.06-4.77), most time "feeling down"(OR = 9.17, 95% CI = 2.94-28.59), reduced libido (OR = 2.90, 95% CI = 1.52-5.52), current anal symptoms (OR = 6.55, 95% CI = 2.54-16.90), recent anal wart diagnosis (OR = 4.33, 95% CI = 1.98-9.49), and fear of developing anal cancer (OR = 9.34, 95% CI = 4.52-19.28).Concerns regarding anal health should be routinely discussed by clinicians, and potentially associated psychosocial, physical, and sexual issues further explored.

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

BACKGROUND: 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. METHOD: 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. RESULTS: 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). CONCLUSIONS: 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.

Sexual behaviours associated with incident high-risk anal human papillomavirus among gay and bisexual men.

OBJECTIVE: High-risk human papillomavirus (HRHPV) causes anal cancer, which disproportionately affects gay and bisexual men (GBM). We examined sexual behaviours associated with incident anal HRHPV in an observational cohort study of GBM in Sydney, Australia. METHODS: GBM aged 35 years and above were enrolled in the Study of the Prevention of Anal Cancer. Detailed information on sexual practices in the last 6 months, including receptive anal intercourse (RAI) and non-intercourse receptive anal practices, was collected. Anal human papillomavirus (HPV) testing was performed at the baseline and three annual follow-up visits. Risk factors for incident HRHPV were determined by Cox regression using the Wei-Lin-Weissfeld method. RESULTS: Between 2010 and 2015, 617 men were recruited and 525 who had valid HPV results at baseline and at least one follow-up visit were included in the analysis. The median age was 49 years (IQR 43-56) and 188 (35.8%) were HIV-positive. On univariable analysis, incident anal HRHPV was associated with being HIV-positive (p<0.001), having a higher number of recent RAI partners regardless of condom use (p<0.001 for both), preference for the receptive position during anal intercourse (p=0.014) and other non-intercourse receptive anal sexual practices, including rimming, fingering and receptive use of sex toys (p<0.05 for all). In multivariable analyses, being HIV-positive (HR 1.46, 95% CI 1.09 to 1.85, p=0.009) and reporting condom-protected RAI with a higher number of sexual partners (p<0.001) remained significantly associated with incident HRHPV. When stratified by recent RAI, non-intercourse receptive anal practices were not associated with incident HRHPV in men who reported no recent RAI. CONCLUSION: GBM living with HIV and those who reported RAI were at increased of incident anal HRHPV. Given the substantial risk of anal cancer and the difficulty in mitigating the risk of acquiring anal HRHPV, HPV vaccination should be considered among sexually active older GBM. TRIAL REGISTRATION NUMBER: ANZCTR365383.

HIV, Immune Dysfunction, and the Natural History of Anal High-Risk Human Papillomavirus Infection in Gay and Bisexual Men.

BACKGROUND: Incidence of anal cancer is highest in gay and bisexual men (GBM). Better understanding of the natural history of anal high-risk human papillomavirus (hrHPV) infection is needed for anal cancer prevention. METHODS: The Study of the Prevention of Anal Cancer was a 3-year study of Australian GBM, aged 35 years or older. We examined incidence, clearance, and risk factors for 13 hrHPV types at baseline and 3 annual visits. RESULTS: In 525 men with ≥ 2 visits, 348 (66.3%) acquired ≥ 1 incident hrHPV infection. HPV16 incidence rates were similar, but non-16 hrHPV incidence was higher in HIV-positive (51.8/100 person years [PY]) than HIV-negative men (36.5/100 PY, P < .001). Annual clearance rates of HPV16 (13.21/100 PY, 95% confidence interval, 10.53-16.56) were lower than for other hrHPV types. hrHPV clearance rates were not associated with HIV overall but were significantly lower in those with a lower nadir CD4 (<200 cells/µL) for HPV16 (P = .015) and other hrHPV types (P = .007). CONCLUSIONS: Higher incidence of non-16 hrHPV types, coupled with lower clearance of non-16 hrHPV types in those with past impaired immune function, is consistent with the greater role of non-16 hrHPV in anal cancer in HIV-positive people. AUSTRALIA NEW ZEALAND CLINICAL TRIALS REGISTRY: ANZCTR365383.

The Natural History of Anal High-grade Squamous Intraepithelial Lesions in Gay and Bisexual Men.

BACKGROUND: Gay and bisexual men (GBM) are disproportionately affected by anal cancer. Prevention is hindered by incomplete understanding of the natural history of its precursor, anal high-grade squamous intraepithelial lesions (HSIL). METHODS: The Study of the Prevention of Anal Cancer, conducted between 2010 and 2018, enrolled human immunodeficiency virus (HIV)-positive and HIV-negative GBM aged ≥35 years. Anal cytology and high-resolution anoscopy (HRA) were performed at baseline and 3 annual visits. A composite HSIL diagnosis (cytology ± histology) was used. Cytological high-grade squamous intraepithelial lesions (cHSIL) incidence and clearance rates were calculated with 95% confidence intervals (CIs). Predictors were calculated using Cox regression with hazard ratios (HRs) and 95% CIs. RESULTS: Among 617 men, 220 (35.7%) were HIV-positive, median age 49 years. And 124 incident cHSIL cases occurred over 1097.3 person-years (PY) follow-up (11.3, 95% CI 9.5-13.5 per 100 PY). Significant bivariate predictors of higher incidence included age <45 years (HR 1.64, 95% CI 1.11-2.41), HIV positivity (HR 1.43, 95% CI .99-2.06), prior SIL diagnosis (P-trend < .001) and human papillomavirus (HPV)16 (HR 3.39, 2.38-4.84). Over 695.3 PY follow-up, 153 HSIL cleared (clearance 22.0, 95% CI 18.8-25.8 per 100 PY). Predictors were age < 45 years (HR 1.52, 1.08-2.16), anal intraepithelial neoplasia (AIN)2 rather than AIN3 (HR 1.79, 1.29-2.49), smaller lesions (HR 1.62, 1.11-2.36) and no persistent HPV16 (HR 1.72, 1.23-2.41). There was 1 progression to cancer (incidence 0.224, 95% CI .006-1.25 per 100 PY). CONCLUSION: These data strongly suggest that not all anal HSIL detected in screening requires treatment. Men with persistent HPV16 were less likely to clear HSIL and are more likely to benefit from effective HSIL treatments. CLINICAL TRIALS REGISTRATION: Australia New Zealand Clinical Trials Registry (ANZCTR365383).

Prevalence of anal cytological abnormalities and high-risk human papillomavirus prevalence in kidney transplant recipients: A cross-sectional study.

BACKGROUND: Transplant recipients are at high-risk of anal squamous cell cancer. We aimed to estimate the prevalence of high-risk human papillomavirus (HPV) and high-grade squamous intraepithelial lesion (HSIL) and assess characteristics associated with results METHODS: We recruited kidney transplant recipients in a single-center, 2015-2018. Participants completed a clinical questionnaire and received an anal-swab sent for HPV-DNA and cytological testing RESULTS: A total of 97 (74%) of 125 recipients approached consented to participate. Participants were median 47 (IQR 40-55) years, 60% male and median 4.5 (IQR .9-13) months-since-transplant. Of 86 assessable samples, at least one HPV genotype was detected in 15 (17%) participants; 1 (1%) HPV16, 8 (9%) other high-risk HPV. Of 76 assessable cytology samples, 9 (12%) showed evidence of abnormality; 1 (1%) HSIL, 1 (1%) atypical-squamous-cells, cannot exclude HSIL. Both HSIL recipients had high-risk HPV and biopsy confirmed HSIL. High-risk HPV was detected in six (9%) recipients with normal cytology. History of sexually transmitted infection, and abnormal cervical pap smear in women, was associated with high-risk HPV and HSIL CONCLUSIONS: High-risk HPV and HSIL testing may identify kidney transplant recipients at higher risk of anal cancer. Longitudinal studies are needed to describe the natural history of anal cancer in transplant recipients.

Self-reported anal symptoms and their association with anal pathology among gay and bisexual men: a cross-sectional observational analysis.

Background Anal symptoms may indicate serious pathology. Receptive anal intercourse (RAI) and sexually transmissible infections (STIs) may contribute to a higher prevalence of symptoms among gay and bisexual men (GBM). This study investigated associations with anal symptoms among GBM. METHODS: The Study of the Prevention of Anal Cancer was a longitudinal study of anal human papillomavirus and related lesions in Sydney, Australia. GBM aged ≥35 years were recruited from community settings between September 2010 and August 2015. Information about anal symptoms (discharge, itch, pain defecating, lump, bleeding, 'sores', tearing, tenesmus), STIs and sexual behaviours was collected. High-resolution anoscopy (HRA) and STI testing were performed. Logistic regression analyses on baseline data were performed to assess associations with each symptom. RESULTS: Among 616 participants (median age 49 years, 35.9% HIV positive), 35.3% reported at least one anal symptom within the past week and 65.3% were diagnosed with fistula, fissure, ulcer, warts, haemorrhoids and/or perianal dermatoses at HRA. Anal symptoms were not associated with anal chlamydia, gonorrhoea, warts or syphilis. Self-reported 'sores' were associated with previous anal herpes simplex virus (HSV; P < 0.001). 'Sores' (P < 0.001), itch (P = 0.019), discharge (P = 0.032) and lump (P = 0.028) were independently associated with ulceration. Among participants diagnosed with fissure, fistulae, haemorrhoids and perianal dermatoses, 61.9%, 100%, 62.0% and 63.9% respectively were asymptomatic. Only self-reported anal tear was independently associated with recent RAI. CONCLUSIONS: Previous anal HSV was the only STI associated with any symptom. Anal pathology was highly prevalent, but often asymptomatic. Anal symptoms do not appear to be useful markers of most anal pathology in GBM.

Psychological and utility-based quality of life impact of screening test results for anal precancerous lesions in gay and bisexual men: baseline findings from the Study of the Prevention of Anal Cancer.

OBJECTIVE: Gay, bisexual and other men who have sex with men (GBMSM), particularly HIV-positive GBMSM, are at increased anal cancer risk compared with the general population. This study examined the psychological and quality of life (QoL) impact of receiving abnormal anal cancer screening results during the baseline visit of the Study of the Prevention of Anal Cancer (SPANC). METHODS: SPANC was a prospective cohort study of the natural history of anal human papillomavirus (HPV) and associated abnormalities in GBM aged 35 years and over. Participants completed questionnaires including aspects of health-related QoL (HR-QoL) and psychosocial functioning at baseline. Participants underwent procedures including an anal swab for cytology, and high-resolution anoscopy with biopsy of any possibly HPV-related abnormality. Questionnaires were readministered 2 weeks and 3 months after participants were given cytology and histology results. Perceived test result served as the study factor. RESULTS: Participants with perceived abnormal results (n=232) reported poorer HR-QoL (mean difference=1.8; p=0.004) and lower utility-based QoL (mean difference=0.02; p=0.018) 2 weeks after screening than individuals with perceived normal results (n=268). These differences did not persist at 3-month follow-up. A greater proportion of participants who perceived their results as abnormal reported feeling worse than usual about their anal health and anal cancer fear (p's<0.001), experienced more intrusive thoughts about their results (p's≤0.006) and felt more likely to develop cancer than other gay men their age (p's≤0.025) at both time points than those with perceived normal results. CONCLUSIONS: Providing abnormal results may cause psychological distress and impact HR-QoL, with sustained intrusive thoughts, increased cancer worry and perceived cancer risk. The potential for psychological harm needs to be considered when implementing anal cancer screening programmes.

Effect of age on the association between recreational drug use and sexual risk behaviour: a cross-sectional observational analysis.

Recreational drug use (RDU) among gay and bisexual men (GBM) is associated with higher-risk sexual behaviours, however this has not been well defined among older GBM. We investigated the association between RDU and sexual behaviours among older GBM in Sydney, Australia. 617 GBM aged 35-79 years self-reported their RDU in the past 6 months and sexual behaviours. Age-stratified univariable associations between RDU and behaviour were examined. GBM aged 35-44 years were the most likely to report RDU, with rates decreasing with increasing age (Ptrend < 0.001). Associations between RDU and higher-risk sexual behaviours were most consistently found among GBM aged 35-54 years.

Prevalence, incidence and predictors of anal Chlamydia trachomatis, anal Neisseria gonorrhoeae and syphilis among older gay and bisexual men in the longitudinal Study for the Prevention of Anal Cancer (SPANC).

OBJECTIVES: Sexually transmitted infection (STI) notifications are increasing among older individuals. Many older gay and bisexual men (GBM) are sexually active and have multiple partners. We aimed to investigate the prevalence, incidence and predictors of anal chlamydia, anal gonorrhoea and syphilis in older GBM. METHODS: The Study for the Prevention of Anal Cancer (SPANC) was a prospective cohort study of HPV infections and related anal lesions among community-recruited GBM age ≥ 35 years in Sydney, Australia. At baseline and subsequent annual visits, recent STI diagnoses were collected via questionnaire ('interval diagnoses') and STI testing occurred ('study visit diagnoses'). Baseline STI prevalence was calculated using study visit diagnoses. Incidence of anal chlamydia and gonorrhoea was calculated using interval and study visit diagnoses. Syphilis incidence was calculated using interval diagnoses. Univariate and multivariate analysis using Cox proportional hazards were undertaken to investigate the association between risk factors and incident STI. RESULTS: Among 617 GBM, the median age was 49 years (range 35-79) and 35.8% (n=221) were HIV-positive. At baseline, STI prevalence was: anal chlamydia 2.3% (n=14); anal gonorrhoea 0.5% (n=3) and syphilis 1.0% (n=6). During 1428 person-years of follow-up (PYFU), the incidence (per 100 PYFU) of anal chlamydia, anal gonorrhoea and syphilis was 10.40 (95% CI 8.82 to 12.25), 9.11 (95% CI 7.64 to 10.85) and 5.47 (95% CI 4.38 to 6.84), respectively. In multivariate analysis, HIV-positivity, higher number of recent condomless receptive anal intercourse partners and baseline methamphetamine use were associated with each STI. Sex with 'fuck-buddies' was associated with anal chlamydia and gonorrhoea. Age was not associated with any STI. DISCUSSION: There was a high incidence of STI among SPANC participants. Age should not be used as a proxy for sexual risk and older GBM require a detailed sexual behaviour and recreational drug use history. Interventions that specifically target STI risk among older GBM should be considered.

Awareness and knowledge of anal cancer in a community-recruited sample of HIV-negative and HIV-positive gay and bisexual men.

Background Anal cancer disproportionately affects people with HIV infection, especially gay and bisexual men (GBM). The awareness and understanding of human papillomavirus (HPV) and anal cancer in a community-based sample of people living with HIV and GBM was explored to inform future evidence-based public health interventions. METHODS: Following consultation with affected communities and relevant healthcare professionals, a questionnaire was developed that assessed knowledge, understanding and experience of anal HPV, HPV vaccination, screening and perceived personal risk of anal cancer. Participants were recruited through HIV community and GBM organisations and anonymously completed the questionnaire online. RESULTS: Of 1660 questionnaires returned, 1574 were analysed from men, of whom 1535 (97.5%) identified as GBM and 15.7% reported being HIV-positive. Most (51.8%) of the HIV-positive men and 68.1% of HIV-negative or unknown men thought their risk of anal cancer was the same, or lower, than that of the general population. Only a small minority (12.5%) reported ever having talked to their doctor about anal HPV and/or anal cancer and 11.6% reported ever having had an anal cancer examination. Less than one-third (31.5%) had heard of HPV vaccination and only 2.9% of men recollected receiving HPV vaccination. CONCLUSIONS: Knowledge and awareness of anal cancer was generally poor in a sample of HIV-positive and HIV-negative GBM. Specific information targeted at these people could potentially raise awareness, leading to earlier diagnosis, reduced burden of disease among GBM and less demands on the healthcare system. Young GBM might benefit from education regarding the importance of HPV vaccination.

Human papillomavirus 16-specific T-cell responses and spontaneous regression of anal high-grade squamous intraepithelial lesions.

BACKGROUND: Most anal cancers are attributable to persistent human papillomavirus type 16 (HPV-16) infection. The anal cancer precursor, high-grade squamous intraepithelial lesion (HSIL), frequently regresses spontaneously. We hypothesized that T-cell responses are associated with HSIL regression. METHODS: In men who have sex with men undergoing anal cytology and high-resolution anoscopy, we measured responses to HPV-16 oncogenic proteins E6 and E7, using the CD25/CD134 assay for CD4(+) antigen-specific T cells and intracellular cytokine staining for CD4(+) and CD8(+) antigen-specific T cells. RESULTS: Of 134 participants (mean [SD] age, 51 [9.3] years; 31 [23.1%] infected with human immunodeficiency virus), 51 (38.1%) had HSIL. E6- and E7-specific CD4(+) T-cell responses were detected in 80 (59.7%) and 40 (29.9%) of the participants, respectively, and E6- and E7-specific CD8(+) T-cell responses were each detected in 25 (18.7%). HSIL was significantly associated with E7-specific CD8(+) T-cell responses (odds ratio, 4.09 [95% confidence interval, 1.55-10.77], P = .004), but not with any CD4(+) T-cell response (P ≥ .09). Twenty-six participants had HSIL a mean of 1 year before measurement of T-cell responses, and 6 (23%) of them were regressors. Five regressors (83%) had E6-specific CD4(+) T-cell responses vs 7 of 20 (35%) nonregressors (Pexact = .065). CONCLUSIONS: Systemic HPV-16 E6- and E7-specific T-cell responses were common in men who have sex with men. E6-specific CD4(+) T-cell responses may be associated with recent HSIL regression. CLINICAL TRIALS REGISTRATION: NCT02007421.

Incidence, clearance, and disease progression of genital human papillomavirus infection in heterosexual men.

BACKGROUND: In this analysis, we examine the incidence and clearance of external genital human papillomavirus (HPV) infection among heterosexual males aged 16-24 years. METHODS: A total of 1732 males aged 16-24 years old in the placebo arm of a quadrivalent HPV vaccine trial were included in this analysis. Participants were enrolled from 18 countries in Africa, the Asia-Pacific region, Europe, Latin America, and North America. Subjects underwent anogenital examinations and sampling of the penis, scrotum, and perineal/perianal regions. RESULTS: The incidence rate of any HPV DNA genotype 6, 11, 16, and/or 18 detection was 9.0 cases per 100 person-years. Rates of HPV DNA detection were highest in men from Africa. Median time to clearance of HPV genotypes 6, 11, 16, and 18 DNA was 6.1, 6.1, 7.7, and 6.2 months, respectively. Median time to clearance of persistently detected HPV 6, 11, 16, and 18 DNA was 6.7, 3.2, 9.2, and 4.7 months, respectively. CONCLUSION: The study results suggest that the acquisition of HPV 6, 11, 16, and/or 18 in males is common and that many of these so-called infections are subsequently cleared, similar to findings for women. Nevertheless, given the high rate of HPV detection among young men, HPV vaccination of males may reduce infection in men and reduce the overall burden of HPV-associated disease in the community.

Human papillomavirus (HPV) genotypes in an Australian sample of anal cancers.

Human papillomavirus (HPV) causes most cases of anal cancers. In this study, we analyzed biopsy material from 112 patients with anal cancers in Australia for the presence of HPV DNA by the INNO LiPA HPV genotyping assay. There were 82% (92) males and 18% (20) females. The mean age at diagnosis was significantly (p = 0.006) younger for males (52.5 years) than females (66 years). HIV-infected males were diagnosed at a much earlier mean age (48.2 years) than HIV negative (56.3 years) males (p = 0.05). HPV DNA was detected in 96.4% (108) of cases. HPV type 16 was the commonest, at 75% (81) of samples and being the sole genotype detected in 61% (66). Overall, 79% (85) of cases had at least one genotype targeted by the bivalent HPV (bHPV) vaccine, 90% (97) by the quadrivalent HPV (qHPV) vaccine and 96% (104) by the nonavalent HPV (nHPV) vaccine. The qHPV vaccine, which is now offered to all secondary school students in Australia, may prevent anal cancers in Australia. However, given the mean age of onset of this condition, the vaccine is unlikely to have a significant impact for several decades. Further research is necessary to prove additional protective effects of the nHPV vaccine.

Anal and perianal squamous carcinomas and high-grade intraepithelial lesions exclusively associated with "low-risk" HPV genotypes 6 and 11.

Anal squamous cell carcinomas are predominantly associated with high-risk human papillomaviruses (HPVs), particularly HPV 16, similar to cervical, vaginal and vulvar cancers. Although the presence of "low-risk" HPVs, in particular genotypes 6 and 11, have occasionally been reported in various HPV-related anogenital cancers, the overall distribution of these genotypes in the anal canal and perianal tissue may differ to that in the cervix. In addition, although the majority of anal and perianal cancers are associated with HPV, some are not; hence, confirmation of direct association of the virus within a lesion is important. Using laser capture microdissection, anal and perianal invasive carcinomas and high-grade squamous intraepithelial lesions (HSILs) in biopsies previously associated with HPV 6 or 11 alone were isolated from tissue sections and HPV genotype tested. Of seven cases tested, four invasive carcinomas were positive for HPV 6 only, one invasive carcinoma was negative for HPV and two HSILs were positive for HPV 11 only. All samples were confirmed as HPV 16/18 negative using two different DNA targets (E6 and L1). From these results, we confirm that HPV 6 and 11 can occasionally be associated with high-grade lesion and anal cancer.

The psychological impact of anal cancer screening on HIV-infected men.

BACKGROUND: Anal cancer rates are increasing in HIV-infected men. Screening programmes similar to prostate and cervical cancer have been recommended to reduce morbidity and mortality. Research shows that screening processes have psychological consequences that need to be considered. Limited investigation of the psychological impact of anal cancer screening has been conducted. METHODS: A prospective longitudinal survey of 291 men was conducted at three time points over 14 weeks at a public HIV clinic in Sydney, Australia. Self-report questionnaires measuring worry, distress, depression, anxiety, stress and health-related quality of life (SF-12) were collected. RESULTS: Those who had a biopsy recommended were significantly more worried about anal cancer, rated their anal health worse and were less optimistic about their future health than the control group who needed no further medical investigation. The group receiving high grade histology results remained worried about anal cancer at time 3. We found no evidence that general anxiety, depression or quality of life was significantly affected by the process. CONCLUSIONS: Anal cancer specific worry increases throughout the screening process. Clear communication prior to procedures about the procedure itself, potential adverse events, the recovery process and non-technical explanations of results should be implemented in anal screening programmes.