The clearance of oral high-risk human papillomavirus infection is impaired by long-term persistence of cervical human papillomavirus infection

Abstract

Persistence of high-risk (HR-) human papillomavirus (HPV) infection of the uterine cervix increases the risk of cervical cancer. Oral HPV infections are among potential covariates of long-term genotype-specific persistent cervical HR-HPV infections. It is not known whether this persistence reflects inability of the host to reject HPV infections in general. A case-control setting was designed to estimate the covariates of long-term persistent cervical HR-HPV infections using multivariate generalized estimating equation (GEE) models. HPV was detected with PCR using GP05+/GP06+-primers and genotyped for 24 HPVs with a Multimetrix-kit. The cases (n=43) included women who had genotype-specific persistent cervical HR-HPV infection for at least 24 months (24M+) and controls were women who tested repeatedly HPV-negative in their cervical samples (n=52). These women represent a sub-cohort of the Finnish Family HPV Study. The cases differed significantly from the HPV-negative controls in several aspects: they were younger, had a longer mean time to incident oral HPV infection (40.7 versus 23.6 months), longer duration of oral HPV persistence (38.4 versus 14.1 months), and longer time to clearance of their oral HPV infection (50.0 versus 28.2 months). In multivariate GEE analysis, the second pregnancy during the follow up was the only independent predictor with significant protective effect against 24M+ persistent cervical HR-HPV infections, OR of 0.15 (95% CI 0.07-0.34). To conclude, long-term persistent cervical HR-HPV infections are associated with a prolonged clearance of oral HR-HPV infections while new pregnancy protects against persistent cervical HR-HPV infections.

Oral manifestations of human papillomavirus infections

“…This indicates that HPV‐16 integration is a common event, even in asymptomatic oral infections, which might predispose the infected subjects to progressive disease . It was also found that in women, persistent (>2 yr) genital HPV infection was predictive for impaired clearance of oral HPV infection . Taken together, our results suggest that long‐term cervical persistence of high‐risk HPV infection might be an indicator of a compromised host response to co‐existent oral HPV infections.…”

Long-term Persistence of Oral Human Papillomavirus Type 16: The HPV Infection in Men (HIM) Study

“…Similar to factors thought to influence HPV persistence at the cervix, our observation of increased oral HPV persistence with age may be due to impairment of host immune responses (24) and elevation of inflammatory cytokines (25) that occur throughout the aging process. In a recent FFHPV study, Louvanto et al demonstrated that oral high-risk HPV infections persist three times longer among women with long-term, persistent cervical HPV infections compared with cervical HPV-negative women (26), suggesting that similar factors may be responsible for increased HPV persistence, regardless of epithelial site of infection. Larger cohort studies are needed to elucidate the biological and behavioral mechanisms underlying oral HPV persistence.…”

The potential impact of prophylactic human papillomavirus vaccination on oropharyngeal cancer

“…17 Other factors that may be associated with persistent infection include high oral HPV viral load 18 and concurrent persistent cervical infection, although long-term natural history data are not available. 19 In comparison, the prevalence of any cervical HPV infection in women in the United States is significantly higher (26.8% for women aged 14-59 years), and 15.2% of women have high-risk cervical HPV infections, with the most common being HPV-16. 11 The peak prevalence of cervical HPV infection is 44.8% in women aged 20 to 24 years, which is a few years after sexual debut ( Fig.…”

“…16 Other factors that may be associated with persistent infection include high oral HPV viral load 17 and concurrent persistent cervical infection, although longterm natural history data are not available. 18 …”