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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. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The American Joint Committee on Cancer (AJCC) staging system undergoes periodic revisions to maintain contemporary survival outcomes related to stage. Recently, the AJCC has developed a novel, systematic approach incorporating survival data to refine stage groupings. The objective of this study was to demonstrate data‐driven optimization of the version 9 AJCC staging system for anal cancer assessed through a defined validation approach. METHODS: The National Cancer Database was queried for patients diagnosed with anal cancer in 2012 through 2017. Kaplan–Meier methods analyzed 5‐year survival by individual clinical T category, N category, M category, and overall stage. Cox proportional hazards models validated overall survival of the revised TNM stage groupings. RESULTS: Overall, 24,328 cases of anal cancer were included. Evaluation of the 8th edition AJCC stage groups demonstrated a lack of hierarchical prognostic order. Survival at 5 years for stage I was 84.4%, 77.4% for stage IIA, and 63.7% for stage IIB; however, stage IIIA disease demonstrated a 73.0% survival, followed by 58.4% for stage IIIB, 59.9% for stage IIIC, and 22.5% for stage IV (p <.001). Thus, stage IIB was redefined as T1‐2N1M0, whereas Stage IIIA was redefined as T3N0‐1M0. Reevaluation of 5‐year survival based on data‐informed stage groupings now demonstrates hierarchical prognostic order and validated via Cox proportional hazards models. CONCLUSION: The 8th edition AJCC survival data demonstrated a lack of hierarchical prognostic order and informed revised stage groupings in the version 9 AJCC staging system for anal cancer. Thus, a validated data‐driven optimization approach can be implemented for staging revisions across all disease sites moving forward. Evaluation of the 8th edition American Joint Committee on Cancer staging system demonstrated a lack of hierarchical prognostic order for anal cancer. Thus, the version 9 American Joint Committee on Cancer staging system for anal cancer was revised through a validated and data‐driven approach and should similarly be applied across all disease sites moving forward. [ABSTRACT FROM AUTHOR]

The World Health Organization recommends human papillomavirus (HPV) testing for cervical screening. Extended genotyping can identify the highest‐risk HPV‐positive women. An inexpensive, rapid, mobile isothermal amplification assay (ScreenFire HPV RS test) was recently redesigned to yield four channels ordered by cancer risk (ie, hierarchical approach): HPV16, HPV18/45, HPV31/33/35/52/58 and HPV39/51/56/59/68. Stored specimens from 2076 women (mean age 30.9) enrolled in a colposcopy clinic, with high HPV prevalence, were tested with ScreenFire. We calculated hierarchical channel positivity and non‐hierarchical channel and type positivity, according to histologic diagnosis (256 cancer, 350 cervical intraepithelial neoplasia [CIN]3, 409 CIN2, 1020 < CIN2) and known virologic reference results (Linear Array and TypeSeq). Additionally, we analyzed ScreenFire time‐to‐positive up to 60 min by channel and histology. Overall clinical sensitivity for CIN3+ was 94.7% (95% confidence interval 92.6‐96.4), similar to Linear Array (92.3, 89.7‐94.3) and TypeSeq (96.0, 93.9‐97.6). Sensitivity was high for all types and channels. The hierarchical approach was well in line with HPV typing and histologic diagnosis, prioritizing higher risk women having HPV16 and precancer. For HPV16, time‐to‐positive was shorter in women with precancer. ScreenFire showed excellent agreement with research reference typing tests and detection of CIN2+. Risk‐based type results could help guide clinical management of HPV‐positive women. Time‐to‐positive combined with genotyping might be useful. ScreenFire is rapid, mobile, relatively inexpensive and designed for implementation of HPV‐based screening and management, including in lower‐resource settings. Further validation in screening by self‐sampling and practical effectiveness merit evaluation. [ABSTRACT FROM AUTHOR]

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including anal cancer, is the standard for cancer staging in the United States. The AJCC staging criteria are dynamic, and periodic updates are conducted to optimize AJCC staging definitions through a panel of experts charged with evaluating new evidence to implement changes. With greater availability of large data sets, the AJCC has since restructured and updated its processes, incorporating prospectively collected data to validate stage group revisions in the version 9 AJCC staging system, including anal cancer. Survival analysis using AJCC eighth edition staging guidelines revealed a lack of hierarchical order in which stage IIIA anal cancer was associated with a better prognosis than stage IIB disease, suggesting that, for anal cancer, tumor (T) category has a greater effect on survival than lymph node (N) category. Accordingly, version 9 stage groups have been appropriately adjusted to reflect contemporary long‐term outcomes. This article highlights the changes to the now published AJCC staging system for anal cancer, which: (1) redefined stage IIB as T1–T2N1M0 disease, (2) redefined stage IIIA as T3N0–N1M0 disease, and (3) eliminated stage 0 disease from its guidelines altogether. [ABSTRACT FROM AUTHOR]

Little is known about risk factors for progression of high‐grade anal intraepithelial neoplasia (AIN) to anal squamous cell carcinoma (ASCC). In this large, population‐based study, we assess the role of factors related to immune status for the risk of ASCC among individuals from the general population with a diagnosis of AIN3. Individuals diagnosed with AIN3 during 1985‐2016 were identified in the Danish Pathology Registry and followed for subsequent development of ASCC. The study population was linked to the National Patient Registry, the Danish Prescription Registry and the Danish HIV Cohort Study for information on autoimmune disease, genital warts and HIV status. To study the progression rate, Cox regression models with hazard ratios (HR) and 95% confidence intervals (CI) were applied with time since AIN3 as the underlying time scale and with adjustment for age at AIN3 diagnosis, year of AIN3 diagnosis and sex. The study population comprised 1222 individuals with AIN3 contributing 12 824 person‐years of follow‐up. Ninety‐seven individuals (7.9%) developed ASCC. Individuals registered with an autoimmune disease or genital warts before and/or after the AIN3 diagnosis had an increased rate of progression to ASCC compared to individuals without these conditions. People living with HIV had a higher progression rate than HIV‐negative individuals (HR = 4.25; 95% CI: 1.87‐9.65) with the highest progression rate among those with CD4 count ≤200 cells/μL. These associations may be caused by an interplay between HPV infection and immunosuppression. [ABSTRACT FROM AUTHOR]

Infection by human papillomavirus (HPV) type 16, the most oncogenic HPV type, was found to be the least affected by HIV‐status and CD4 count of any of the approximately 13 oncogenic HPV types. This relative independence from host immune status has been interpreted as evidence that HPV16 may have an innate ability to avoid the effects of immunosurveillance. However, the impact of immune status on other individual HPV types has not been carefully assessed. We studied type‐specific HPV infection in a cohort of 2,470 HIV‐positive (HIV[+]) and 895 HIV‐negative (HIV[−]) women. Semi‐annually collected cervicovaginal lavages were tested for >40 HPV types. HPV type‐specific prevalence ratios (PRs), incidence and clearance hazard ratios (HRs), were calculated by contrasting HPV types detected in HIV[+] women with CD4 < 200 to HIV[−] women. HPV71 and HPV16 prevalence had the weakest associations with HIV‐status/CD4 count of any HPV, according to PRs. No correlations between PRs and HPV phylogeny or oncogenicity were observed. Instead, higher HPV type‐specific prevalence in HIV[−] women correlated with lower PRs (ρ = −0.59; p = 0.0001). An alternative (quadratic model) statistical approach (PHIV+ = a*PHIV− + b*PHIV−2; R2 = 0.894) found similar associations (p = 0.0005). In summary, the most prevalent HPV types in HIV[−] women were the types most independent from host immune status. These results suggest that common HPV types in HIV[−] women may have a greater ability to avoid immune surveillance than other types, which may help explain why they are common. What's new? What makes common types of human papillomavirus (HPV) common? To answer this question, the authors examined HPV types in HIV‐infected and uninfected women as the immune status in this population is quantifiable by CD4 T cell count. They found that HPV types that were most prevalent in HIV‐negative women were also the types whose prevalence was least affected by HIV infection. This relative independence from immune status supports a model that the innate ability to avoid the effects of immune surveillance makes common HPV types, in fact, common. [ABSTRACT FROM AUTHOR]

Although anogenital cancers have been on a gradual rise in developing countries in the past few decades, they have been understudied. The objective was to investigate genotypic diversity of anogenital HPV amongst women reporting for routine cervical cancer screening in Harare in Zimbabwe. A cross-sectional study that enrolled 144 women ≥18 years from a cervical cancer-screening clinic was performed. Each woman provided a self-collected cervico-vaginal swab (VS) and a clinician-collected anal swab (CCAS). HIV testing was offered and cervical cytology was performed. Both VS and CCAS samples were HPV genotyped, using amplicon sequencing of the L1 gene region with Illumina technology. Mean age of the women was 39.9 (range 18-83 years, SD ± 11.0). HPV prevalence was 72% (104/144) in VS and 48% (69/144) in CCAS. The most common genotypes detected in both VS and CCAS were HPV18, HPV52, and HPV16. Sixty two percent of the subjects had multiple genotypic HPV infections. The odds of being HPV-positive among HIV-infected women were higher than in HIV-negative women in both the vagina and the anus (CCAS OR = 4.8; CI 2.4-9.8, P < 0.001) and (VS OR = 2.9; CI 1.3-6.4, P = 0.005). High HPV prevalence and diverse genotypes were detected in both the vagina and anus. Anal oncogenic HPV infection was common. HPV 52 was one of the most common oncogenic genotypes in both the vagina and anus. HIV co-infection played a significant role in the prevalence of HPV. These data have implications for design of primary and secondary programs for prevention of anogenital cancer in Zimbabwe. [ABSTRACT FROM AUTHOR]

Background Little is known about the association between oral and anogenital human papillomavirus (HPV) infections. Methods Oral and anal samples from 66 men who have sex with men with a history of HPV-related anogenital squamous intraepithelial lesions were analyzed using polymerase chain reaction (PCR), and typed for 38 HPV types. Results Prevalence of oral HPV infection was 30%, versus 82% for anal infection. Prevalence of oral and anal high-risk HPV infection was 11% and 64%, respectively. Concurrent oral-anal any-type HPV infection was found in 26% of participants, whereas concordant type-specific HPV prevalence was 5%. In multivariate analysis, number of partners from whom the participant received oral-penile sex and number of partners on whom the participant performed oral-penile sex were associated with oral HPV infection. Conclusion Oral HPV prevalence in this cohort is high, however, concordant type-specific oral-anal HPV infection was rare. Increased risk of oral HPV infection was associated with oral-penile sex. © 2015 Wiley Periodicals, Inc. Head Neck 38: E399-E405, 2016 [ABSTRACT FROM AUTHOR]

The incidence of anal cancer is elevated in human immunodeficiency virus (HIV)-infected men-who-have-sex-with-men (MSM) compared to the general population. Anal high-grade squamous intraepithelial lesions (HSIL) are common in HIV-infected MSM and the presumed precursors to anal squamous cell cancer; however, direct progression of HSIL to anal cancer has not been previously demonstrated. The medical records were reviewed of 138 HIV-infected MSM followed up at the University of California, San Francisco, who developed anal canal or perianal squamous cancer between 1997 and 2011. Men were followed up regularly with digital anorectal examination (DARE), high-resolution anoscopy (HRA) and HRA-guided biopsy. Although treatment for HSIL and follow-up were recommended, not all were treated and some were lost to follow-up. Prevalent cancer was found in 66 men. Seventy-two HIV-infected MSM developed anal cancer while under observation. In 27 men, anal cancer developed at a previously biopsied site of HSIL. An additional 45 men were not analyzed in this analysis due to inadequate documentation of HSIL in relation to cancer location. Of the 27 men with documented progression to cancer at the site of biopsy-proven HSIL, 20 men progressed from prevalent HSIL identified when first examined and seven men from incident HSIL. Prevalent HSIL progressed to cancer over an average of 57 months compared to 64 months for incident HSIL. Most men were asymptomatic, and cancers were detected by DARE. Anal HSIL has clear potential to progress to anal cancer in HIV-infected MSM. Early diagnosis is facilitated by careful follow-up. Carefully controlled studies evaluating efficacy of screening for and treatment of HSIL to prevent anal cancer are needed. [ABSTRACT FROM AUTHOR]

BACKGROUND Although screening of human immunodeficiency virus (HIV)-positive individuals for anal intraepithelial neoplasia (AIN; a precursor of anal cancer) has been practiced in San Francisco among HIV health care providers since the early 1990s, to the authors' knowledge no study to date has focused on evaluating recent AIN trends. METHODS Cases of high-grade AIN 3 and invasive anal cancer from 2000 to 2009 were obtained from the San Francisco/Oakland Surveillance, Epidemiology, and End Results (SEER) population-based cancer registry. Age-standardized rates of AIN 3 and anal cancer were calculated overall and by demographic characteristics (sex, race, and age group). Log-linear regression calculated annual percent change in rates during 2000 to 2009, and rate ratios (RRs) and 95% confidence intervals (95% CIs), evaluated differences in rates during 2000 through 2004 and 2005 through 2009. RESULTS During 2000 through 2009, the majority of AIN 3 cases occurred among men (1152 of 1320 men; 87.3%). Rates of AIN 3 during the corresponding period increased by 11.48% per year ( P < .05) among men and were stable among women. Comparing rates among men during 2000 to 2004 with those during 2005 to 2009, the largest increases were noted among those aged 50 years to 64 years (RR, 2.47; 95% CI, 1.93-3.17) and among black individuals (RR, 3.49; 95% CI, 2.14-5.85). During the same period, anal cancer rates were stable among men and women. CONCLUSIONS Rates of AIN 3 increased in San Francisco during 2000 through 2009, in conjunction with an anal cytology screening program for high-risk groups, whereas rates of invasive anal cancer were unchanged. Continued surveillance is necessary to evaluate the impact of screening and human papillomavirus vaccination on the prevention of human papillomavirus-related AIN and anal cancer. Cancer 2013;119:3539-3545.. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) 58 accounts for a notable proportion of cervical cancers in East Asia and parts of Latin America, but it is uncommon elsewhere. The reason for such ethnogeographical predilection is unknown. In our study, nucleotide sequences of E6 and E7 genes of 401 HPV58 isolates collected from 15 countries/cities across four continents were examined. Phylogenetic relationship, geographical distribution and risk association of nucleotide sequence variations were analyzed. We found that the E6 genes of HPV58 variants were more conserved than E7. Thus, E6 is a more appropriate target for type-specific detection, whereas E7 is more appropriate for strain differentiation. The frequency of sequence variation varied geographically. Africa had significantly more isolates with E6-367A (D86E) but significantly less isolates with E6-203G, -245G, -367C (prototype-like) than other regions ( p ≤ 0.003). E7-632T, -760A (T20I, G63S) was more frequently found in Asia, and E7-793G (T74A) was more frequent in Africa ( p < 0.001). Variants with T20I and G63S substitutions at E7 conferred a significantly higher risk for cervical intraepithelial neoplasia grade III and invasive cervical cancer compared to other HPV58 variants (odds ratio = 4.44, p = 0.007). In conclusion, T20I and/or G63S substitution(s) at E7 of HPV58 is/are associated with a higher risk for cervical neoplasia. These substitutions are more commonly found in Asia and the Americas, which may account for the higher disease attribution of HPV58 in these areas. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is detected in nearly all cervical cancers and approximately half of vaginal cancers. However, vaginal cancer is an order of magnitude less common than cervical cancer, not only in the general population but also among women with HIV/AIDS. It is interesting therefore that recent studies found that HPV was common in both normal vaginal and cervical tissue, with higher prevalence of nononcogenic HPV types in the vagina. In our investigation, we prospectively examined HPV infection in 86 HIV-positive and 17 HIV-negative women who underwent hysterectomy during follow-up in a longitudinal cohort. Cervicovaginal lavage specimens were obtained semi-annually and tested for HPV DNA by polymerase chain reaction. To address possible selection biases associated with having a hysterectomy, subjects acted as their own comparison group-before versus after hysterectomy. The average HPV prevalence was higher in HIV-positive than HIV-negative women both before (59% vs. 12%; p < 0.001) and after hysterectomy (56% vs. 6%; p < 0.001). Multivariate random effects models (within-individual comparisons) demonstrated significantly lower HPV prevalence [odds ratio (OR) = 0.71; 95% confidence interval (CI) = 0.59-0.85) after hysterectomy. The association of HPV prevalence with hysterectomy was similar among HIV-positive and HIV-negative women. However, hysterectomy had greater effects on oncogenic (OR = 0.48; 95% CI = 0.35-0.66) than nononcogenic HPV types (OR = 0.89; 95% CI = 0.71-1.11; Pinteraction = 0.002). Overall, we observed greater reductions in oncogenic than nononcogenic HPV prevalence after hysterectomy. If correct, these data could suggest that oncogenic HPV have greater tropism for cervical compared to vaginal epithelium, consistent with the lower incidence of vaginal than cervical cancer. [ABSTRACT FROM AUTHOR]

A systematic review was conducted of HPV type distribution in anal cancer and anal high-grade and low-grade squamous intraepithelial lesions (HSIL and LSIL). A Medline search of studies using PCR or hybrid capture for HPV DNA detection was completed. A total of 1,824 cases were included: 992 invasive anal cancers, 472 HSIL cases and 360 LSIL cases. Crude HPV prevalence in anal cancer, HSIL, and LSIL was 71, 91 and 88%, respectively. HPV16/18 prevalence was 72% in invasive anal cancer, 69% in HSIL and 27% in LSIL. The HPV 16 and/or 18 prevalence in invasive anal cancer cases was similar to that reported in invasive cervical cancer. If ongoing clinical trials show efficacy in preventing anal HPV infection and associated anal lesions, prophylactic HPV vaccines may play an important role for the primary prevention of these cancers in both genders. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Proliferative verrucous leukoplakia (PVL) is a recently described clinical entity characterized by multifocal oral lesions that frequently progress to oral cancer despite abstinence from tobacco use by most patients. To determine if this condition is associated with human papillomavirus (HPV), a polymerase chain reaction (PCR) for HPV DNA was performed on 9 lesions from 7 patients with PVL, histologically diagnosed with focal keratosis (1), papilloma (1), epithelial dysplasia (5) and squamous cell cancer (2). Eight (89%) were HPV positive, 7 for HPV 16. For comparison, we studied 55 non-PVL-associated oral specimens, including 24 oral squamous cell cancers. Of the cancers, 8 (33%) were FIPV positive, 4 for HPV 16. These data suggest that HPV 16 infection may play an important role in the pathogenesis of PVL-associated oral dysplasia and possibly cancer, but is found in only a small proportion of the more common, non-PVL associated-oral lesions. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is one of the most common sexually transmitted infections and a significant cause of anogenital malignancies, precancer lesions, and cutaneous disease. Human immunodeficiency virus (HIV)-positive individuals have a higher prevalence of HPV infection and HPV-associated anogenital disease compared to age-matched HIV-negative controls. Data suggest that there has been little reduction in HPV-associated disease since the introduction of highly active antiretroviral therapy (HAART). The authors believe that cervical and anal cancer screening using Pap tests should be offered to all HIV-positive individuals, but the infrastructure to identify (via colposcopy and high-resolution anoscopy) and treat precancer lesions must be present. Treatment of HPV-associated anogenital disease depends on the size, location, and grade of the lesion, whereas a variety of ablative and excisional therapies are available. Prophylactic and therapeutic HPV vaccines are promising as future interventions for disease control in at-risk populations such as HIV-infected women and men.