Genetic variants of human papillomavirus types 16 and 18 (HPV16/18) could differ in their cancer risk. We studied the prevalence and association with high-grade cervical lesions of different HPV16/18 variant lineages in a case-control study including 217 cases (cervical intraepithelial neoplasia grade 2 or grade 3 or worse: CIN2 or CIN3+) and 116 controls (no CIN2 or CIN3+ in two-year follow-up). HPV lineages were determined by sequencing the long control region (LCR) and the E6 gene. Phylogenetic analysis of HPV16 confirmed that isolates clustered into previously described lineages: A (260, 87.5%), B (4, 1.3%), C (8, 2.7%), and D (25, 8.4%). Lineage D/lineage A strains were, respectively, detected in 4/82 control patients, 19/126 CIN3+ cases (OR = 3.1, 95%CI: 1.0–12.9, p = 0.04), 6/1 glandular high-grade lesions (OR = 123, 95%CI: 9.7–5713.6, p<0.0001), and 4/5 invasive lesions (OR = 16.4, 95%CI: 2.2–113.7, p = 0.002). HPV18 clustered in lineages A (32, 88.9%) and B (4, 11.1%). Lineage B/lineage A strains were respectively detected in 1/23 control patients and 2/5 CIN3+ cases (OR = 9.2, 95%CI: 0.4–565.4, p = 0.12). In conclusion, lineages A of HPV16/18 were predominant in Spain. Lineage D of HPV16 was associated with increased risk for CIN3+, glandular high-grade lesions, and invasive lesions compared with lineage A. Lineage B of HPV18 may be associated with increased risk for CIN3+ compared with lineage A, but the association was not significant. Large well-designed studies are needed before the application of HPV lineage detection in clinical settings.

BackgroundHigh risk human papillomavirus (HR-HPV) infection in males is a health issue with implications for HPV-related lesions in their partners. The identification of risk factors for male infection may improve our understanding of HR-HPV transmission and prevention. The aim of this study was to evaluate the relationships between lifestyle, genital warts and HR-HPV infection. The study was focused on men with an increased risk of HR-HPV infection: male sexual partners of women diagnosed with high-grade squamous intraepithelial cervical lesions.MethodsMen were enrolled and prospectively recruited within the first six months after diagnosis of cervical lesions in their female partners (n = 175, 2013–2016). Epidemiological and sexual behaviour data were obtained. The presence of genital warts was established by visual inspection. Detection and genotyping of HR-HPV infection in genital samples were performed with a Linear Array HPV Genotyping Test. All HR-HPV positive men were offered a follow-up exam at 12 months. SPSS version 19 was used for statistical analysis.Results and discussionThe prevalence of HR-HPV infection in men was 45.1% (79/175). Genital warts were observed in 10.3% (18/175) of the subjects. Detection of genital warts (OR 3.5, p = 0.015), smoking habits (OR 2.3, p = 0.006) and sexual debut before 16 years old (OR 2, p = 0.035) were associated with an increased risk for HR-HPV infection (univariate analysis). This association was also observed for genital warts and smoking status in a multivariate analysis. The same genotype was found after one year in 71.4% (20/28) of subjects.ConclusionsThe presence of genital warts and smoking habits seem to be associated with a higher risk of HR-HPV infection in males. Earlier sexual debut may increase this risk. Extensive knowledge of the natural history of HR-HPV infection in males is an absolute requirement for the design and implementation of prevention strategies for the general population as well as for specific populations such as couples after treatment for high-grade cervical lesions.

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BackgroundHuman papillomavirus (HPV) bivalent and quadrivalent vaccines have been widely implemented in worldwide organized immunization programs. A nonavalent HPV vaccine is now available in several countries. The objective was to describe the fraction of squamous non-invasive high-grade cervical intraepithelial lesions attributable to genotypes targeted by bi-quadrivalent vaccines and by nonavalent vaccine according to age and diagnosis in women living in the city of Vigo (Galicia, Spain).MethodsCervical scrapings (2009–2014) of women with histological diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2, n = 145) and grade 3-carcinoma in situ (CIN3-CIS, n = 244) were tested with Linear Array HPV Genotyping test (Roche diagnostics, Mannheim, Germany). Hierarchical estimation of the fraction attributable to HPV 16/18 or HPV 31/33/45/52/58 detected alone or in combination was calculated. Absolute additional fraction attributable to genotypes targeted by nonavalent vaccine compared to genotypes targeted by bi-quadrivalent vaccines was calculated as the increment of attributable cases with respect to all studied cases. Age group 1, 2 and 3 included women 18 to 34, 35–44 and ≥45 years old, respectively. EPIDAT 3.1 was used.ResultsFraction attributable to genotypes targeted by bi-quadrivalent vaccines was 59% CIN2 vs. 69% CIN3-CIS (p < 0.001). It was 63/51/50% of CIN2 and 78/66/45% of CIN3-CIS in age group 1, 2, 3, respectively. Fraction attributable to genotypes targeted by nonavalent vaccine was 86% CIN2 and 86% CIN3-CIS. It was 87/91/75% of CIN2 and 90/86/76% of CIN3-CIS in age group 1, 2, 3, respectively. Fraction attributable to genotypes targeted by these vaccines tended to decrease as age increased (p-trend <0.05). Globally, absolute additional attributable fraction was 16%, 26% and 29% in age group 1, 2 and 3, respectively (p < 0.005).ConclusionsAbsolute additional fraction of CIN2 and CIN3-CIS attributable to genotypes targeted by nonavalent vaccine was observed in women of any age, especially in those over 35 years old.

A better understanding of human papillomavirus (HPV) infection in men is an essential component of prevention programs aimed to reduce cervical cancer and other HPVrelated diseases. A screening test capable of detecting asymptomatic/subclinical genital HPV infection in men at a reasonable price and causing minimal discomfort to the patient would be very valuable. The following chapter focuses on acetowhite test usefulness in the detection of asymptomatic/subclinical genital high-risk (HR) HPV infection in highrisk men populations, HR-HPV prevalence in sexually active healthy male partners of women diagnosed of high-grade cervical intraepithelial neoplasia and genotypespecific concordance between partners, addressing the preventive strategies that would reduce HPV infection in men. We present data from 125 men, sexual partners of women with preneoplastic cervical lesions. Prevalence of HR-HPV infection in male was high (50, 24% HPV16) and genotype concordance within the 60 infected couples was remarkable (62% shared at least one genotype). Acetowhite (AW) test was positive in 27% patients, showing low sensitivity for the identification of HR-HPV infection but allowed the diagnosis of subclinical HPV-related lesions in more than 10%. Current smoking and genital warts were associated with an increased risk of HR-HPV infection in men (OR: 2.4 and 5.6, respectively).

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