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BACKGROUND: Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV)-related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied. METHODS: Two hundred and sixty MSMLWH aged 18-26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24. RESULTS: Among 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type-associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18-associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events. CONCLUSIONS: 18-26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type-associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.

Objective: Anal cancer precursor lesions high-grade anal intraepithelial neoplasia (HGAIN) are highly prevalent among HIV+ MSM. Treatment of HGAIN is frustrated by high recurrence rates. We investigated the efficacy of the quadrivalent human papillomavirus (qHPV) vaccine as posttreatment adjuvant in preventing HGAIN recurrence in HIV+ MSM. Design: Randomized, double-blind, placebo-controlled, multicentre trial. Setting: Three HIV outpatient clinics in Amsterdam, the Netherlands. Subjects: HIV+ MSM with CD4+ cell count more than 350 cells/μl, biopsy-proven intra-anal HGAIN successfully treated in the past year, and lesions still in remission at enrolment, as assessed by high-resolution anoscopy (HRA). Intervention: Participants were randomized to three doses of qHPV (Gardasil-4, MSD) or placebo with vaccinations at 0, 2, and 6 months. HRA was repeated at 6, 12, and 18 months. Main outcome measure: The primary outcome was cumulative, biopsy-proven HGAIN recurrence rate at 18 months, evaluated in an intention-to-treat (ITT) (received all vaccinations) and per-protocol analysis (all vaccinations and complete follow-up). Results: We randomized 126 participants of which 64 (50.8%) received qHPV and 62 (49.2%) placebo. All participants received three vaccinations, and in both groups for two participants follow-up was incomplete. We found no difference (P = 0.38) in cumulative HGAIN recurrence rates between the qHPV (44/64, 68.8%) and placebo group (38/62, 61.3%) in the ITT analysis [absolute risk reduction −7.5 (95% confidence interval (CI) −24.1 to 9.2)]. This was similar in the per-protocol analysis. Conclusion: Despite adequate serological responses to qHPV vaccination, short-term recurrence of HGAIN was not prevented. These findings do not support qHPV vaccination as a treatment adjuvant to prevent HGAIN recurrence in HIV+ MSM.

Background Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV)–related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied. Methods Two hundred and sixty MSMLWH aged 18–26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24. Results Among 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type–associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18–associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events. Conclusions 18–26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type–associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination., A high proportion of 18-26 year-old men-who-have-sex-with-men-living-with-HIV screened for a quadrivalent HPV (qHPV) vaccine trial had anal low-grade/high-grade squamous intraepithelial lesions (LSIL/HSIL). Vaccinees naive to qHPV types were protected against incident qHPV type-associated-LSIL/HSIL. Vaccination before sexual initiation is critically important.

Background: Anal squamous intraepithelial lesions (ASIL) are precancerous lesions of anal squamous cell carcinoma, with a higher prevalence in immunosuppressed patients. There are some studies in kidney transplant recipients, but there is no information regarding prevalence in liver transplantation. Our aim was to evaluate the prevalence of ASIL in this setting. Methods: Prospective case–control study involving liver transplant recipients without any other known risk factor for ASIL (n=59), which were compared with a healthy control group (n=57). All were submitted to anal cytology and high-resolution anoscopy was performed in those with abnormal results. Results: Ten (17%) of liver transplant recipients had abnormal cytological results, seven patients had atypical squamous cells of undetermined significance (ASC-US), one patient had atypical squamous cells that cannot exclude high-grade (ASC-H) and two patients had high-grade squamous intraepithelial lesions (HSIL). In the control group, one patient (2%) had an ASC-US result (P=0.005). Anal squamous intraepithelial lesions were confirmed in 7 out of 10 of liver transplant patients and 0 out of 1 in the controls (P=0.013) by high-resolution anoscopy with biopsies. Current smoking was the only risk factor for abnormal cytology (odds ratio=5.87, 95% confidence intervals=1.22–28.12, P=0.027). Conclusions: Liver transplant patients have a higher risk of ASIL. Screening should be considered, especially in smokers.

Histological grading of squamous intraepithelial lesions or intraepithelial neoplasia is fundamental for clinical management and for assessment of the risk of progression. Biomarkers are important for assisting correct grading of these lesions, reducing inter and intraobserver variability and most promising, for prognosis. Although p16 is the most studied biomarker in this setting, there are several other biomarkers that have been studied, reflecting also the need to find a better single or association option that can be more suitable, especially for classification purposes. A PubMed and Embase search was conducted from their inception until April 2018, aiming to identify biomarkers evaluated in histological samples of anal squamous intraepithelial lesions, other than p16. Information on “Ki-67”, “ProEx™ C”, “p53”, “human papillomavirus L1 capsid protein”, “stathmin-1”, “minichromosome maintenance protein”, “p21”, “proliferating cell nuclear antigen”, “histones”, “human papillomavirus E4”, “chromosomal abnormalities” and “methylation” was collected and reviewed. From these, the most studied biomarker was by far Ki-67. In many cases there were few studies performed for each biomarker, with no clear standardized interpretation of the immunostaining. An increased positive rate with more severe grades of lesions was shown in many cases. Prognostic data are limited and need to be further validated.

Background An association between HPV infection and progression to anal squamous intraepithelial lesions (ASIL) has been established, specifically in high-risk populations such as HIV-infected men. In this population, anal cancer is one of the most common non-AIDS-defining malignancies. Methods A cross-sectional study to detect anal lesions and HPV infection was performed. Anal mucosa samples were collected from 56 HIV-infected men from Cuba. The cytological diagnosis was done according to Bethesda 2001 System. HPV DNA detection was determined by qPCR for six high-risk HPV types and end point PCR for low-risk HPV types (6 and 11). The end point PCR with nucleotide sequencing technique was achieved to detect other genotypes of HPV not included in the qPCR in those samples negative for HPV- 6 and 11 or negative for the six genotypes identified in the qPCR. Results Cytological diagnosis identified 53 of 56 (95%) men with abnormal anal cytology. Among those, 26% (14/53) had atypical squamous cells of undetermined significance (ASC-US), 4% (2/53) had atypical squamous cells of undetermined significance cannot exclude high-grade lesions (ASC-H), 64% (34/53) had low-grade squamous intraepithelial lesions (LSIL), and 6% (3/53) had high-grade squamous intraepithelial lesions (HSIL). HPV DNA was detected in 89% (50/56) of men and 79% had at least one of the high-risk HPV types. HPV- 16 was the most common genotype (52%), while HPV-18 was the most frequently detected genotype in men with HSIL. We found statistically significant differences in the HPV viral loads with respect to the cytology results (p = 0.0006) and that the practice of receptive anal sex was a risk factor for anal HPV infection (p = 0.032). Conclusion This study shows a high prevalence of ASIL and high-risk HPV infections in the study group and is the first study showing the distribution of HPV genotypes in HIV infected Cuban men with abnormal anal cytology. This information may be of importance for local decision makers to improve prevention strategies, including the introduction of HPV vaccine in Cuba.

Background We studied anal specimens to determine the distribution of human papillomavirus (HPV) genotypes and co-infection occurrence. This information will contribute to the knowledge of HPV genotype distributions and provide an estimate of the prevalence of different oncogenic HPV genotypes found in patients in Madrid (Spain). Methods We studied a total of 82 anal biopsies from the Hospital General Universitario Gregorio Marañón of Madrid. These included 4 specimens with benign lesions, 52 specimens with low-grade anal squamous intraepithelial lesion, 24 specimens with high-grade anal squamous intraepithelial lesions and 2 specimens with invasive anal carcinoma. HPV genotyping was performed with PCR amplification and reverse dot blot hybridization. Results We detected 33 different HPV genotypes, including 16 HPVs associated with a high risk of carcinogenesis, 3 HPVs associated with a highly likely risk of carcinogenesis and 14 HPVs associated with a low-risk of carcinogenesis. In two specimens, an uncharacterized HPV genotype was detected. The most frequent HPV genotypes found were HPV-16 (10.3%; 95% CI: 6.6%-15.1%), HPV-52 (8.5%; 95% CI: 5.2%-13%) and HPV-43/44 (7.6%; 95% CI: 4.5%-11.9%). HPV-18 was only detected in 0.9% (95% CI: 0.1%-3.2%) of the total viruses detected in all lesions. HPV co-infections were found in 83.9% of all types of lesions. The majority of cases (90.2%) were concomitantly infected with the human immunodeficiency virus (HIV). Conclusion The prevalence of high-risk carcinogenic genotypes in anal pathological samples was remarkable. Therefore, further studies that include a greater number of samples, particularly invasive carcinoma cases are needed to evaluate the potential influence of these HPV genotypes in the appearance of anal carcinomas. Also, the influence of other accompanying infections should be evaluated clarify the appearance of this type of carcinoma. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2075238024106058.