Might Oral Human Papillomavirus (HPV) Infection in Healthy Individuals Explain Differences in HPV-Attributable Fractions in Oropharyngeal Cancer? A Systematic Review and Meta-analysis

Abstract

Background: Differences in oral human papillomavirus (HPV) prevalence and contrasts in HPV-attributable fractions (AFs) in oropharyngeal cancer (OPC) have not been evaluated in depth.

Methods: A systematic review was performed to identify studies in which at least 50 healthy individuals were tested for oral HPV infection. Information on sex, age, tobacco/alcohol consumption, sex practices, specimen collection, HPV detection, and population type was extracted. Prevalences were pooled using random-effects models for meta-analyses of binomial data. Correlations were assessed by the Spearman test.

Results: Forty-eight reports comprising 28 544 individuals fulfilled inclusion criteria. Global oral HPV prevalence was 4.9%. Estimates were highest in Europe, although regional differences were not statistically significant. HPV16 prevalence was 1.0% globally, and regional differences became statistically significant. A lifetime history of >6 sex partners showed a higher risk of oral HPV infection. The age-specific HPV distribution revealed a prevalence of ≥5% over 40 years of age and a lower prevalence at younger ages. There was no association between oral HPV prevalence and HPV-AFs or age-standardized rates (ASRs) of OPC, genital HPV in healthy women, or tobacco use.

Conclusions: Differences in HPV-AFs or ASRs of OPC cannot be explained by differences in the prevalence of oral HPV infection across healthy populations. Consistent research on determinants of oral HPV prevalence, acquisition, clearance, and persistence is warranted.

Keywords: HPV infection; Oral; head and neck cancer; healthy population; meta-analysis.

Figure 1.

Prevalence of oral human papillomavirus (HPV) infection overall (A), due to high-risk types (B), and due to HPV16 (C), by region. Regional estimates and heterogeneity between groups have been estimated only for regions with >500 individuals. However, the global estimates include all studies testing >50 individuals. CI, confidence interval.

Figure 2.

Distribution of oral human papillomavirus (HPV) types, by region. CI, confidence interval.

Figure 3.

Distribution of studies on the overall prevalence of oral human papillomavirus (HPV) infection, by country. Each square corresponds to a study included in the meta-analysis. The size of the squares is proportional to the size of the study. The distribution of the squares within each country is arbitrary and does not correspond to the recruitment area of the studies.

Figure 4.

Age-specific prevalence of oral human papillomavirus infection overall. CI, confidence interval.

Figure 5.

Correlation between oral human papillomavirus type 16 (HPV16) infection and HPV-attributable fraction (AF) of oropharyngeal cancer (OPC) (A), age-standardized incidence rate (ASR) of HPV-associated head and neck cancer (HNC) (B), genital HPV16 infection in healthy women (C), and smoking prevalence (D), by country . Countries with outlying estimates were excluded. Estimates for HPV-AFs were derived from Castellsagué et al [12] for all regions except North America, Southern Africa, Northern Africa, and Australia and New Zealand AFs. For North America, AFs were derived from Jordan et al [32]; for Southern and Northern Africa, AFs were derived from de Martel et al [13]; and for Australia and New Zealand, AFs were derived from Hong et al [33]. Estimates of ASRs of HPV-related HNC in 2012 were derived from de Martel et al [13]. Estimates for genital HPV prevalence in healthy women were derived from Bruni et al (unpublished data). Estimates for tobacco use in 2006 were derived from Ng et at [6].