Natural history of oral papillomavirus infections in spouses: A prospective Finnish HPV Family Study

Abstract

Background

The natural history of genital human papillomavirus infection is well known, but nearly nothing is known about the outcome of oral HPV-infection.

Objectives and study design

To study natural history of oral HPV in spouses during the follow-up 331 women (mean 25.5 ± 3.4 years) and 131 men (mean 28.8 ± 5.0 years) were recruited from maternity unit. Scrapings from healthy oral mucosa of spouses at baseline, 2, 6, 12 and 24 months and genital samples were taken for HPV testing. HPV DNA was detected by nested PCR and confirmed by hybridization using a cocktail of 12 high-risk (HR) oligoprobes.

Results

The detection rate of HR HPVs varied from 15% to 27%. Baseline oral HPV status between the spouses was closely related (odds ratio 4.3; 95% confidence interval 1.6–12.0; P = 0.006). Persistent oral infection in one spouse was a significant risk factor (odds ratio 10.0; 95% confidence interval 1.5–68.7; P = 0.005) for oral HR HPV persistence in the other partner. Cumulative incidence of new HR HPV infections was identical in both spouses, while men seemed to clear their infection more rapidly. In univariate survival analysis, the partner's oral or genital HPV status, oral sex habits or age did not predict clearance or acquisition of oral HR HPV.

Conclusion

Natural history of HPV infection in oral mucosa mimics that of genital HPV infection. Oral sex had no association to oral HPV infection, but a persistent oral HPV infection of the spouse increased the risk of persistent oral HPV infection 10-fold in the other spouse.

Introduction

In oral mucosa, human papillomavirus (HPV) is associated with several benign lesions including condyloma accuminatum, papilloma, focal epithelial hyperplasia, verruca vulgaris (reviewed in Syrjänen and Syrjänen, 2000, Syrjänen, 2003). In 1983 we showed first evidence that HPV infection might be etiologically related to of oral cancers (Syrjänen et al., 1983). Recent meta-analysis and case-control studies have confirmed HPV infection as a risk factor for head and neck cancer with odd ratios of 3.7–5.4 (Syrjänen and Syrjänen, 2000, Miller and Johnstone, 2001, Herrero et al., 2003). Similar to genital mucosa, HPV is also detected in clinically healthy oral mucosa in 10–13% of the adult population as reported in a meta-analysis or literature survey until 1997 (reviewed in Syrjänen and Syrjänen, 2000, Miller and Johnstone, 2001, Syrjänen, 2003). At least 37 of the 106 different HPV types have been detected in oral mucosa; HPV 16 being the most common type, followed by HPV 6 (Syrjänen and Syrjänen, 2000, Syrjänen, 2003, Kreimer et al., 2004, Cañadas et al., 2004).

The origins of oral HPV infection are not fully elucidated yet. Sexual transmission explains oral HPV infections poorly, because the oral and genital HPV types of partners are different in most published studies (Kellokoski et al., 1992a, Kellokoski et al., 1992b). Similarly, oral and genital mucosas were shown to harbour different HPV types in women, simultaneously (Kellokoski et al., 1992a, Badaracco et al., 1998, Bennedetti Panici et al., 1998, Cañadas et al., 2004). Frequent detection of skin warts concomitantly with oral HPV DNA might suggest the possibility of hand-to-oral transmission (Kellokoski et al., 1992b, Terai et al., 1999), which parallels the findings of hand–genital transmission (Fairley et al., 1995, Sonnex et al., 1999). Apart from sexual transmission and auto-inoculation, other possible HPV transmission modes are horizontal transmission, vertical transmission and transmission via fomites or saliva (Syrjänen and Puranen, 2000).

To shed more light on the dynamics of HPV transmission within a family, we set up the prospective Finnish HPV Family Study, assessing the modes of HPV spread among infants and their parents (Rintala et al., 2005). The present report is the first prospective study, where the natural history of high-risk (HR) HPV and acquisition and clearance rates were analyzed in healthy oral mucosa of spouses followed-up for two years.