Human papillomavirus in premalignant oral lesions: No evidence of association in a Spanish cohort

PLoS One. 2019 Jan 16;14(1):e0210070. doi: 10.1371/journal.pone.0210070. eCollection 2019.


Background: Human papillomavirus (HPV) is the cause of a fraction of head and neck squamous cell carcinoma. Although this relation is well-known, it is still not clear the role of HPV in premalignant oral lesions such as oral lichen planus (OLP) and dysplasia. We aimed to evaluate the HPV-DNA prevalence and type distribution in a set of oral biopsies obtained from patients diagnosed with OLP and dysplasia, as well as the role of HPV in these lesions.

Methods: A retrospective cohort of all premalignant oral lesions consecutively diagnosed from March 30th 1995 to May 21st 2014 at Hospital of Bellvitge and Odontological University Hospital of Bellvitge was identified and classified in four groups: OLP (groups 1 and 2) and dysplasias (groups 3 and 4) that progressed or not to invasive cancer during follow-up. A random selection targeting 25 cases was aimed to be performed for each group. All selected cases were subjected to pathological evaluation, DNA quality control and HPV-DNA detection. HPV-DNA positive samples were further subject to p16INK4a analysis.

Results: A total of 83 cases yielded a valid HPV-DNA result. From those, 7 and 34 cases were OLP that progressed or not to invasive cancer during follow-up, whereas 24 and 18 cases were displasias that progressed or not to invasive cancer during follow-up, respectively. HPV-DNA was detected in 4 samples (3 dysplastic lesions and 1 OLP). Two samples were HPV16 positive (2%), 1 sample HPV18 positive (1%) and 1 sample (1%) was HPV indeterminate. Two out of four HPV-DNA positive cases had high p16INK4a expression and none of the HPV positive cases progressed to invasive cancer during long-term follow-up.

Conclusions: We found a low HPV-DNA attributable fraction in premalignant lesions of the oral cavity, suggesting that HPV is unlikely to play a significant role in oral carcinogenesis in our setting.

MeSH terms

  • Aged
  • Carcinogenesis
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • Female
  • Humans
  • Lichen Planus, Oral / pathology*
  • Lichen Planus, Oral / virology
  • Male
  • Middle Aged
  • Mouth / pathology*
  • Mouth / virology
  • Mouth Neoplasms / diagnosis
  • Mouth Neoplasms / virology
  • Papillomaviridae / classification
  • Papillomaviridae / genetics
  • Papillomaviridae / physiology
  • Papillomavirus Infections / pathology*
  • Papillomavirus Infections / virology
  • Precancerous Conditions / pathology*
  • Precancerous Conditions / virology
  • Retrospective Studies
  • Spain


  • DNA, Viral

Grants and funding

The authors received no specific funding for this work.