Human papillomavirus (HPV) types 16, 18, 31, 45 DNA loads and HPV-16 integration in persistent and transient infections in young women

<p>Abstract</p> <p>Background</p> <p>HPV burden is a predictor for high-grade cervical intraepithelial neoplasia and cancer. The natural history of HPV load in young women being recently exposed to HPV is described in this paper.</p> <p>Methods</p> <p>A total of 636 female university students were followed for 2 years. Cervical specimens with HPV-16, -18, -31, or -45 DNA by consensus PCR were further evaluated with type-specific and β-globin real-time PCR assays. Proportional hazards regression was used to estimate hazard ratios (HR) of infection clearance. Generalized estimating equations assessed whether HPV loads was predictive of HPV infection at the subsequent visit.</p> <p>Results</p> <p>HPV loads were consistently higher among women <25 years old, and those who had multiple sex partners, multiple HPV type infections and smokers. HPV-16 integration was encountered only in one sample. Infection clearance was faster among women at lower tertiles of HPV-16 (HR = 2.8, 95%CI: 1.0-8.1), HPV-18 (HR = 3.5, 95%CI: 1.1-11.2) or combined (HR = 2.4, 95%CI: 1.8-6.2) DNA loads. The relationship between HPV-16 and HPV-18 DNA loads and infection clearance followed a clear dose-response pattern, after adjusting for age and number of sexual partners. GEE Odds Ratios for HPV persistence of the middle and upper tertiles relative to the lower tertile were 2.7 and 3.0 for HPV-16 and 3.8 and 39.1 for HPV-18, respectively. There was no association between HPV-31 or -45 DNA loads and persistence.</p> <p>Conclusions</p> <p>The association between HPV load and persistence is not uniform across high-risk genital genotypes. HPV-16 integration was only rarely demonstrated in young women.</p

Defining the genetic susceptibility to cervical neoplasia - a genome-wide association study

Funding: MAB was funded by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship. Support was also received from the Australian Cancer Research Foundation. JL holds a Tier 1 Canada Research Chair in Human Genome Epidemiology. The Seattle study was supported by the following grants: NIH, National Cancer Institute grants P01CA042792 and R01CA112512. Cervical Health Study (from which the NSW component was obtained) was funded by NHMRC Grant 387701, and CCNSW core grant. The Montreal study was funded by the Canadian Institutes of Health Research (grant MOP-42532) and sample processing was funded by the Reseau FRQS SIDA-MI. The Swedish Research Council, the Swedish Foundation for Strategic Research, the ALF/LUA research grant in Gothenburg and Umeå, the Lundberg Foundation, the Torsten and Ragnar Soderberg’s Foundation, the Novo Nordisk Foundation, and the European Commission grant HEALTH-F2-2008-201865-GEFOS, BBMRI.se, the Swedish Society of Medicine, the KempeFoundation (JCK-1021), the Medical Faculty of Umeå University, the County Council of Vasterbotten (Spjutspetsanslag VLL:159:33-2007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PDFPublisher PD

The laboratory diagnosis of genital human papillomavirus infections

Human papillomaviruses (HPVs) are the etiological agents of several genital cancers, including cancer of the uterine cervix. The detection of HPV infection in genital samples may increase the sensitivity of primary and secondary screenings of cervical cancer. HPV testing may also improve the specificity of screening programs, resulting in the avoidance of overtreatment and cost savings for confirmatory procedures. The major determinants of clinical progression of HPV infection include persistence of HPV infection, involvement of high-risk HPV types, high HPV viral load, integration of viral DNA and presence of several potential cofactors. Signal amplification HPV-DNA detection techniques (Hybrid Capture II, Digene Corporation, USA) are standardized, commercially available, and capable of detecting several high-risk HPV types. They also increase the sensitivity of screening for high-grade lesions in combination with cytology. The sensitivity of these techniques to detect high-grade lesions is higher than that of cytology, but the referral rate for colposcopy is greater. These techniques are approved for the triage to colposcopy of women with cervical smears interpreted as atypical squamous cells of undetermined significance. Triage and screening for cervical cancer using HPV will probably be restricted to women aged 30 years or older because of the high prevalence of infection in younger women. Amplification techniques are ideal for epidemiological studies because they minimize the misclassification of HPV infection status. These techniques can detect low HPV burden infections. Consensus primers amplify most genital types in one reaction, and the reverse hybridization of amplicons with type-specific probes allows for the typing of HPV-positive samples. Consensus PCR assays are currently under evaluation for diagnostic purposes. HPV testing is currently implemented for the clinical management of women

Persistence of human papillomavirus 16, 18 and 52 variants in Inuit women from Northern Quebec, Canada

Intratypic DNA polymorphism has been described for human papillomavirus (HPV) types infecting Inuit women in Nunavik, Quebec, a high-risk population for HPV infection and cervical cancer, but there is no previous research on the association between HPV polymorphism and infection persistence in Inuit women. Polymorphism of HPV types 16, 18 and 52 was described in a subset of 64 participants with multiple clinic visits within a cohort of 677 Nunavik Inuit women aged 15–69 recruited in 2002–2010 with testing results. Logistic regression and Cox proportional hazards models were used to assess the association between HPV variants and infection persistence and clearance. Infections with HPV16 lineage A3 variants cleared 3.13 times faster (95% CI: 1.10–8.97) than those with lineage A1 variants. HPV52 lineage C variants cleared slower than lineage A variants (HR = 0.28, 95% CI: 0.08–0.98). HPV polymorphism may be associated with viral persistence for certain HPV types in this population

Human Papillomavirus Type 16 Viral Load Is Higher in Human Immunodeficiency Virus-Seropositive Women with High-Grade Squamous Intraepithelial Lesions Than in Those with Normal Cytology Smears

Human papillomavirus type 16 (HPV-16) viral load in cervicovaginal lavage samples collected from 66 human immunodeficiency virus-seropositive women was inversely correlated with blood CD4 count (P = 0.002). HPV-16 viral load was 81-fold higher in women with cervical smears suggestive of high-grade lesions (median, 4,425,883 copies/μg of DNA) than in women with normal smears (median, 54,576), controlling for age (P = 0.006)

Two-years persistence of anal high-risk HPV infections in women living with HIV, results from the EVVA study

Background: Women living with HIV are at increased risk of anal high-grade squamous intraepithelial lesions (HSIL) and anal cancer because of higher persistence of high-risk HPV (HR-HPV) infection. This study describes the persistence of type-specific anal HR-HPV over two years. Methods: EVVA (Evaluation of HPV, HIV, and AIN in women) is a cohort study of 151 adult women living with HIV in Montreal (Canada), with biannual cervical/anal HPV testing and cytology for 2 years and at two systematic high-resolution anoscopies for all participants. Only participants who completed 2 study visits were included in this analysis (n=135). Results: Persistent anal infection by at least one HR-HPV was observed in 40.7% of participants (55/135, 95% confidence interval (CI) 32.4–49.5), persisting for 2 years in majority. Persistent HPV-16 was observed in 10.4% (14/135, 95%CI 5.8–16.8), detected for 2 years in 13 women. HPV-18 persisted in 6.7% (95%CI 3.1–12.3), HPV-45 in 11.1% (95%CI 6.4–17.7), HPV-51 in 11.9% (95%CI 6.9–18.5), HPV-52 in 8.9% (95%CI 4.7–15.0) and HPV-58 in 7.4% (95%CI 3.6–13.2). Anal histological HSIL was detected in 50.9% (28/55, 95%CI 37.1–64.6) of women with persistent HR-HPV infection by at least one type, and in 15.0% (12/80, 95%CI 8.0–24.7) of women who never had. Conclusions: Our study confirms that persistence of anal HR-HPV is common in women living with HIV, most of the persistent infections being identified for at least 2 years. Anal HSIL is detected more frequently in women with persistent anal HR-HPV