Dataset Information

Presence of multiple genotypes in subjects with HPV-16 infection is highly associated with anal squamous intraepithelial lesions in HIV-1 infected males.

ABSTRACT: The aim of the study was to determine the prevalence of abnormal cytological findings, high risk (HR)-HPV genotypes and to identify factors associated with an abnormal cytological findings in a cohort of HIV-infected males.Retrospective observational study on HIV-infected male patients who performed screening in the absence of clinical symptoms. Cytological abnormalities were classified as atypical squamous cells of undetermined significance (ASC-US), low-grade(LSIL) or high high-grade squamous intraepithelial lesion (HSIL). Logistic regression models were used to identify predictors of having LSIL/HSIL.Among 875 pts, abnormal cytology findings were observed in 254 (29%, 95% CI: 26.1%-32.1%) subjects: 142 (16%) had LSIL and 49 (6%) HSIL. Overall, 581 (66%, 95%CI: 63.2%-69.5%) subjects had ?1 HR-HPV type and 269 (31%) had ?2 HR HPV types. Multivariate logistic regression showed that subjects with multiple HR-HPV genotypes (OR = 1.351, 95%CI: 1.005-2.111) and with HPV-16 type (OR = 2.032, 95%CI: 1.313-3.146) were more likely to have LSIL/HSIL in addition to a lower CD4+/CD8+ ratio, a previous diagnosis of syphilis and a positive viral load. In another multivariate model, the presence of multiple HPV types in subjects with HPV-16 type was associated with the highest adjusted OR of having a LSIL/HSIL (OR = 2.598, 95%CI: 1.460-4.624).In HIV-infected men, the prevalence of abnormal cytological findings was of 29% and of HR-HPV was 66%. The concomitant presence of HPV-16 and multiple HR genotypes was associated with an increased risk of abnormal cytological findings. These data highlight the importance of screening multiple HPV genotypes in HIV-infected patients.

SUBMITTER: Rovelli C

PROVIDER: S-EPMC5663371 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Presence of multiple genotypes in subjects with HPV-16 infection is highly associated with anal squamous intraepithelial lesions in HIV-1 infected males.

Rovelli Cristina C Poli Andrea A Galli Laura L Cernuschi Massimo M Tamburini Andrea Marco AM Racca Sara S Tambussi Giuseppe G Rolla Serena S Albarello Luca L Rosati Riccardo R Lazzarin Adriano A Castagna Antonella A Nozza Silvia S

PloS one 20171031 10

<h4>Objectives</h4>The aim of the study was to determine the prevalence of abnormal cytological findings, high risk (HR)-HPV genotypes and to identify factors associated with an abnormal cytological findings in a cohort of HIV-infected males.<h4>Patients and methods</h4>Retrospective observational study on HIV-infected male patients who performed screening in the absence of clinical symptoms. Cytological abnormalities were classified as atypical squamous cells of undetermined significance (ASC-U ...[more]

PMID: 29088236

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Project description:BackgroundLittle is known about the epidemiological characteristics of papillomavirus (HPV) infection among North African countries. Herein, we conducted a molecular epidemiological study to investigate prevalence of HPV type and HPV-16 variants among cervical-screened unvaccinated Tunisian women.MethodsCross-sectional study was performed on 494 Tunisian women visiting Women's Healthcare Centers. HPV-DNA detection was carried out on cervical samples using real-time polymerase chain reaction. HPV genotyping and HPV-16 variants were characterized by direct sequencing of L1 viral capsid gene.ResultsThe overall HPV prevalence was 34% (95% CI: 30-38%) with significantly higher prevalence among women with squamous intraepithelial lesions (SIL) than those with no intraepithelial lesions (NIL) 84% (95% CI: 76-92%) and 24.5% (95% CI: 20-29%) respectively. The distribution of HPV prevalence according to women's age shows a U-shaped curve and the highest HPV prevalence rates were observed among the youngest (≤25 years; 51.2%, 95% CI: 37-67%) and the oldest women (>55 years; 41.7%, 95% The HPV-16 prevalence was 32.8% (95% CI: 22-45%) among women with SIL and 9.2% (95% CI: 6-12%) among women with NIL. Whereas, the HPV-18 prevalence was 1.3% (95% CI: 0-5%) among women with SIL and 0.3% (95% CI: 0-1%) among women with NIL. Among HPV-16 positive women, European lineage (E) was identified as the predominant HPV-16 variant (85.7%, 95% CI: 76-95%). The frequency of E variant was lower among SIL than among NIL women (81%, 95% CI: 64-99%, and 88%, 95% CI: 77-100%, respectively). Conversely, the African-2 variant frequency was higher among SIL than among NIL women (18%, 95% CI: 1-36% and 6%, 95% CI: 2-14%, respectively). In multivariate analysis, young age was the only risk factor that is independently associated with HPV infection. Moreover, HPV infection and menopause were both found to be independently associated with SIL and HSIL.ConclusionHPV DNA testing should be proposed to young and menopausal Tunisian women. Considering HPV prevalence, only 13% of the Tunisian women could be protected by the bivalent HPV vaccine. These results may be helpful for designing an adapted HPV testing and vaccination program in Tunisia.

Project description:BackgroundThe incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking.MethodsWe conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer.ResultsOf 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test).ConclusionsAmong participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).

Project description:ObjectivesBecause current guidelines recognise high-grade anal squamous intraepithelial lesions (HSILs) and low-grade SILs (LSILs), and recommend treatment of all HSILs although not all progress to cancer, this study aims to distinguish transforming and productive HSILs by grading immunohistochemical (IHC) biomarkers p16INK 4a (p16) and E4 in low-risk human papillomavirus (lrHPV) and high-risk (hr)HPV-associated SILs as a potential basis for more selective treatment.MethodsImmunostaining for p16 and HPV E4 was performed and graded in 183 biopsies from 108 HIV-positive men who have sex with men. The causative HPV genotype of the worst lesion was identified using the HPV SPF10-PCR-DEIA-LiPA25 version 1 system, with laser capture microdissection for multiple infections. The worst lesions were scored for p16 (0-4) to identify activity of the hrHPV E7 gene, and panHPV E4 (0-2) to mark HPV production and life cycle completion.ResultsThere were 37 normal biopsies, 60 LSILs and 86 HSILs, with 85% of LSILs caused by lrHPV and 93% of HSILs by hrHPV. No normal biopsy showed E4, but 43% of LSILs and 37% of HSILs were E4 positive. No differences in E4 positivity rates were found between lrHPV and hrHPV lesions. Most of the lesions caused by lrHPV (90%) showed very extensive patchy p16 staining; p16 grade in HSILs was variable, with frequency of productive HPV infection dropping with increasing p16 grade.ConclusionsCombined p16/E4 IHC identifies productive and nonproductive HSILs associated with hrHPV within the group of HSILs defined by the Lower Anogenital Squamous Terminology recommendations. This opens the possibility of investigating selective treatment of advanced transforming HSILs caused by hrHPV, and a 'wait and see' policy for productive HSILs. What's already known about this topic? For preventing anal cancer in high-risk populations, all patients with high-grade squamous intraepithelial lesions (HSILs) are treated, even though this group of lesions is heterogeneous, the histology is variable and regression is frequent. What does this study add? By adding human papillomavirus (HPV) E4 immunohistochemistry to p16 INK4a (p16), and grading expression of both markers, different biomarker expression patterns that reflect the heterogeneity of HSILs can be identified. Moreover, p16/E4 staining can separate high-risk HPV-associated HSILs into productive and more advanced transforming lesions, providing a potential basis for selective treatment.

Project description:ObjectiveTo estimate the prevalence, incidence and persistence of anal HPV infection and squamous intra-epithelial lesions (SILs) among men living with HIV (MLHIV), and determine their risk factors.MethodsWe enrolled MLHIV ≥18 years, who attended 6-monthly visits for 18 months. Socio-behavioural data were collected by questionnaire. Clinicians collected blood sample (CD4+ count and HIV plasma viral load), anal swabs (HPV DNA testing) and anal smears (Bethesda classification) at each visit. HPV DNA testing and classification of smears were done at enrolment and last follow-up visit (two time points). Factors associated with persistent anal HPV infection and SILs were evaluated with generalized estimating equations logistic regression and standard logistic regression respectively.ResultsMean age of 304 participants was 38 (Standard Deviation, 8) years; 25% reported >1 sexual partner in the past 3 months. Only 5% reported ever having sex with other men. Most (65%) participants were taking antiretroviral treatment (ART), with a median CD4+ count of 445 cells/μL (IQR, 328-567). Prevalence of any-HPV infection at enrolment was 39% (88/227). In total, 226 men had anal HPV DNA results at both enrolment and final visits. Persistence of any-anal HPV infection among 80 men who had infection at enrolment was 26% (21/80). Any persistent anal HPV infection was more frequent among MLHIV with low CD4+ count (<200 vs. >500 cells/μL; aOR = 6.58; 95%CI: 2.41-17.94). Prevalence of anal SILs at enrolment was 49% (118/242) while incidence of SILs among MLHIV who had no anal dysplasia at enrolment was 27% (34/124). Of the 118 men who had anal dysplasia at enrolment, 15% had regressed and 38% persisted by month 18. Persistent anal HPV infection was associated with persistent SILs (aOR = 2.95; 95%CI: 1.08-10.89). ART status or duration at enrolment were not associated with persistent anal HPV infection or persistent SILs during follow-up.ConclusionIn spite of a high prevalence of anal HPV, HIV-positive heterosexual men have a low burden of anal HPV related disease. HPV vaccine and effective ART with immunological reconstitution could reduce this burden of infection.

Dataset Information

Presence of multiple genotypes in subjects with HPV-16 infection is highly associated with anal squamous intraepithelial lesions in HIV-1 infected males.

Publications

Presence of multiple genotypes in subjects with HPV-16 infection is highly associated with anal squamous intraepithelial lesions in HIV-1 infected males.

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