Katja Kero

Oral Mucosa as a Reservoir of Human Papillomavirus: Point Prevalence, Genotype Distribution, and Incident Infections Among Males in a 7-year Prospective Study

BACKGROUND In addition to the anogenital malignancies, human papillomavirus (HPV) has been linked to oropharyngeal cancer as an important risk factor in both men and women. Knowledge of oral HPV infection among males is needed to elucidate the transmission routes and potential for prevention. OBJECTIVE To assess the prevalence, genotype distribution, and incidence of oral HPV infections among healthy Finnish men followed for 7 yr. DESIGN, SETTING, AND PARTICIPANTS Oral scrapings for HPV testing were taken from 131 fathers-to-be (mean age: 28.9 yr) at baseline and at 2-mo, 6-mo, 12-mo, 24-mo, 36-mo, and 7-yr follow-up visits to detect prevalent and incident HPV infections. Purified DNA extracted from scrapings was used for HPV genotyping, with the Multimetrix kit (Progen Biotechnik, Heidelberg, Germany) detecting 24 genotypes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Point prevalence, genotype distribution, and incident rates of oral HPV infections. Demographic data were collected using structured questionnaires, and covariates of incident oral HPV infections were analysed using uni- and multivariate Poisson regression (for panel data). RESULTS AND LIMITATIONS The point prevalence of oral HPV infection fluctuated from 15.1% to 31.1% during the follow-up period. In total, 17 different HPV genotypes were found. At baseline, the single most frequent genotype among the HPV-positive samples was HPV16 (33.3%; 8 of 24), followed by HPV33 (12.5%) and HPV82 (12.5%). Multiple-type infections comprised 16.7% (4 of 24), HPV16 being involved in all combinations. For baseline-negative men, the mean time to the first incident infection ranged from 3.9 mo (HPV82) to 25.7 mo (HPV56). None of the demographic factors was a significant independent predictor of incident oral HPV infections in multivariate models. CONCLUSIONS Detection of oral HPV DNA carriage in men is common, HPV16 being the most prevalent genotype. Oral mucosa may play a significant role in HPV transmission.

Physical state and copy numbers of HPV16 in oral asymptomatic infections that persisted or cleared during the 6-year follow-up

Persistent human papillomavirus (HPV) infection is a key event in HPV-induced carcinogenesis. As part of the prospective Finnish Family HPV Study, we analysed the physical state and viral copy numbers of HPV16 in asymptomatic oral infections that either persisted or cleared during the 6-year follow-up. The persister group comprised 14 women and 7 men with 51 and 21 HPV16-positive brush samples. The clearance group included 41 women and 13 men, with 64 and 24 samples, respectively. Physical state and viral DNA load were assessed by using quantitative PCR for HPV16 E2 and E6 genes. E2/E6 ratio was calculated and HPV16 was classified as episomal, mixed or integrated with values of 0.93-1.08, <0.93 and 0, respectively. In both genders, the physical state of HPV16 was significantly different between the cases and controls (P<0.001). HPV16 was episomal in all men and 66 % (27/41) of women who cleared their infection. HPV16 was mixed and/or integrated in71 % and 57 %of the women and men persisters, respectively. The mean HPV16 copy number per 50 ng genomic DNA was nearly 5.5-fold higher in the women than in the men clearance group (P=0.011). Only in men, HPV16 copy numbers were higher in persisters than in the clearance group (P=0.039). To conclude, in both genders, persistent oral HPV16 infections were associated with the mixed or integrated form of HPV16, while in the clearance groups, episomal HPV16 predominated. This indicates that HPV16 integration is a common event even in asymptomatic oral infections, which might predispose the infected subjects to progressive disease.

Association of asymptomatic bacterial vaginosis with persistence of female genital human papillomavirus infection

More data are needed on the role of abnormal vaginal microbiota in the natural history of cervical human papillomavirus (HPV) infections. Our purpose was to study the prevalence of mixed flora (MF), bacterial vaginosis (BV) and yeast infection in women with known HPV outcomes during the 72-month follow-up (FU). Asymptomatic pregnant women (N = 329) were enrolled in the third trimester of their pregnancy. Pap smears and HPV genotyping samples were taken at baseline and at 12-, 24-, 36- and 72-month FU visits, with one additional sample at 2 months for HPV. HPV testing was done with nested PCR and Multimetrix assay to determine the point prevalence and persistence of HPV. Conventional Pap smears were scored for MF, BV and yeast infection. Covariates of the outcomes were analyzed using generalized estimating equation (GEE) and Poisson regression. Of the women, 76.6% (252/329) tested HPV-positive at least once during the FU. BV was detected in 12.2% (40/329), MF in 57.4% (189/329) and yeast infection in 22.9% (73/329) of the women. HPV-positive women had significantly more leucocytes in their Pap smear (p = 0.023) than the HPV-negative ones. MF (OR 2.75, 95% CI 1.77–4.27) and yeast infection (p = 0.007) were linked with HPV positivity. BV but not yeast infection was a significant covariate of HPV persistence (p = 0.024; OR 2.15, 95% CI 1.13–4.08). MF and yeast infection were associated with prevalent cervical HPV infection. In the longitudinal setting, BV predicted HPV persistence, implicating that treatment of asymptomatic BV in women with cervical HR-HPV infections might be justified.

Herpes simplex and human papilloma virus coinfections in oral mucosa of men—A 6-year follow-up study

Herpes simplex virus (HSV) establishes latency in neurons and recurrent infections in oral mucosa. This prospective study analyzes HSV prevalence in oral mucosal brush samples from men with known human papillomavirus (HPV) status. We hypothesized that HSV‐1‐infection could facilitate HPV persistence as a cofactor. This study was a part of the Finnish Family HPV study accomplished at the University of Turku/Turku University Hospital, Finland. A total of 139 men (mean age 28.6 ± 4.9 years) were enrolled at 36+‐weeks of their partners pregnancy and thereafter followed‐up for 6 years. Altogether, 722 samples, extracted from oral brush samples collected at the enrollment timepoint (baseline) and at 2‐, 6‐, 12‐, 24‐, 36‐month, and 6 years, were available. HSV DNA was analyzed with quantitative PCR. HSV‐1 results were compared with the known HPV data. The prevalence of oral HSV‐1 shedding varied between 0‐7.2% (mean 2.8%) among the men. Mean copy numbers varied between 4 and 550 genome copies/sample. A total of 18 (12.9%) men were found HSV‐1‐positive at least once, two of them twice. Neither smoking nor oral sex was associated with the oral HSV‐1‐DNA finding. HPV/HSV‐1 co‐infection was found in 6 (4.3%) men, all of them having persistent HPV‐infection. In conclusion, HSV‐1 and its coinfection with HPV in oral mucosa was rare.