Approximately, 20% the of head and neck squamous cell carcinomas (HNSCC) are associated with HPV, except for oropharyngeal SCC, of which nearly 60% are HPV-related. Although HPV has been settled as an etiological factor of a subgroup of these cancers, we still lack the natural history data showing the progression of HPV infection from asymptomatic lesions to intraepithelial neoplasia and cancer. However, meta-analysis covering case-control studies have shown that HPV is four times more likely to be present in oral potentially malignant lesions than in healthy oral mucosa (Syrjänen et al. 2012). The meta-analysis by Jayaprakash et al. (2011) showed no significant difference in HPV-16/18 prevalence rates (around25%) between the dysplastic lesions and cancers in one hand, or between mild, moderate or severe dysplasia. They also reported that HPV was three times more likely to be present in male dysplastic lesions or SCC than in respective lesions in women.
So far, there are only two on-going follow-up (FU) studies on oral HPV infections: our Finnish Family HPV Study (FFHPV) on 331 families with six-year FU and HIM study on 23 men with oral HPV16 followed for 3-years. In the FFHPV totally 329 families were enrolled, comprising 329 mothers, 131 fathers and 331 newborns. The women were originally enrolled in the cohort at 36-weeks (minimum) of their index pregnancy and subsequently the parents and child to-come were followed up (FU) for 6 years.
In our FFHPV study, point prevalence of oral HPV varied from 15% to 24% and 15% to 31% in women and men with 18 and 17 HPV genotypes, respectively. Most of the persisting oral infections in males were caused by HPV16. Smoking increased while previous genital warts decreased oral HR-HPV persistence. Altogether, 71.6% of the men cleared their infection. In women, HPV16 and HPV6 were the two most common genotypes and these were also the most likely to persist. Use of oral contraceptives and a second pregnancy protected against oral HPV persistence. Increased clearance was related with older age and a history of atopic reactions, whereas previous sexually transmitted disease and new pregnancy were associated with decreased clearance. The protective factors for incident oral HPV-species 7/9 infections were 1) new pregnancy during FU, and 2) having the same sexual partner during FU. Persistent oral HPV16 infections in both genders are clearly associated with mixed or integrated physical state of the virus, while most of the cleared HPV16 infections are of episomal state.
Oral HPV infection is common in adults. HPV integration is import for HPV persistence and represents an early event in oral carcinogenesis.
Jayaprakash V et al. Human papillomavirus types 16 and 18 in epithelial dysplasia of oral cavity and oropharynx: a meta-analysis, 1985-2010.Oral Oncol. 2011 Nov;47(11):1048-54.
Syrjänen S et al. Human papillomaviruses in oral carcinoma and oral potentially malignant disorders: a systematic review.Oral Dis. 2011 Apr;17 Suppl 1:58-72.