Latency of tobacco smoking for head and neck cancer among HPV-positive and HPV-negative individuals

Int J Cancer. 2020 Jul 1;147(1):56-64. doi: 10.1002/ijc.32708. Epub 2019 Oct 23.


Human papillomavirus (HPV) infection and tobacco smoking are well-known risk factors for head and neck cancers (HNC). Although an effect modification between oral HPV infection and tobacco smoking may exist, evidence is lacking on how they interact temporally. We investigated the latency and life course effects of tobacco smoking on risk of HNC among HPV-positive (HPV+ve ) and negative (HPV-ve ) individuals. We used data from 631 ever-smoker participants of a hospital-based case-control study conducted in four major hospitals in Montréal, Canada. Cases (n = 320), incident, histologically confirmed, primary squamous cell carcinomas, were frequency-matched to controls (n = 311) by age and sex. Sociodemographic and behavioral factors (e.g., tobacco and alcohol use and sexual history) were collected using a structured interview applying a life grid technique. Oral exfoliated cells were used for HPV DNA detection and genotyping. Latency effects were estimated flexibly using a Bayesian relevant exposure model and further extended with a life course approach. Retrospective smoking trajectories for HPV+ve cases and controls had similar shapes. Exposure to tobacco smoking even 40 years before diagnosis was associated with an increased HNC risk among both HPV+ve and HPV-ve participants. The effect of smoking before the start of sexual activity compared to afterwards was higher among HPV+ve individuals. This pattern of association was less profound among HPV-ve participants. Temporal interactions may exists between oral HPV infection and life course smoking trajectories in relation to HNC risk.

Keywords: Bayesian inference; head and neck cancer; latency effect; tobacco smoking.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Canada / epidemiology
  • Case-Control Studies
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • Female
  • Head and Neck Neoplasms / epidemiology*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / virology
  • Humans
  • Male
  • Middle Aged
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / epidemiology*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Sexual Behavior / statistics & numerical data
  • Squamous Cell Carcinoma of Head and Neck / epidemiology*
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Squamous Cell Carcinoma of Head and Neck / virology
  • Tobacco Smoking / epidemiology*
  • Tobacco Smoking / pathology


  • DNA, Viral