Combined effects of smoking and HPV16 in oropharyngeal cancer

Abstract

Background: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood.

Methods: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multi-centre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression.

Results: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer.

Conclusions: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.

Keywords: Human papillomavirus; head and neck cancer risk; interaction; oropharynx cancer; tobacco smoking.

Figure 1.

Main effects for smoking, alcohol and HPV16 antibodies and oropharyngeal cancer risk. For HPV16, corresponding antibody negatives were considered the reference. ^† 30 controls and 1 OPC patient were missing smoking status information, and 416 controls and 25 OPC patients were missing data on frequency of alcohol consumption. *ORs adjusted for age, sex, smoking status (never, former, current), alcohol consumption (never, ever drinkers g per day as continuous variable) and country as appropriate.

Figure 2.

Estimated prevalence of oropharyngeal cancer by smoking and HPV16 status. he prevalence of oropharyngeal cancer by categories of smoking and HPV16 was calculated based on ORs from a model including interaction terms between smoking categories and HPV16 E6-positivity, and an assumed population prevalence of 0.003.