Detection of human papillomavirus (HPV)-16 in the oral cavity may be associated with 22-times increased risk of oropharyngeal squamous cell carcinoma, according to a study published in JAMA Oncology.1

The researchers for this study also found positive associations of other oral HPVs usually detected on the skin with the risk of head and neck squamous cell carcinoma (HNSCC).1

The researchers theorized that the role of HPV in HNSCC may be more important than currently recognized. In addition, these new findings may lead to new vaccine approaches for preventing HNSCC.


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“In this study, we examined prospectively associations between detection of a wide spectrum of oral HPVs (alpha, beta, and gamma) with incident head and neck cancers in a nested case-control study among approximately 97 000 participants who provided mouthwash samples in 2 large cohort studies.

Oral HPV16 detection, which preceded cancer development on average for 4 years, was associated with a 22-fold increased risk of incident oropharyngeal cancer,” said study investigator Ilir Agalliu, MD, ScD, who is an assistant professor of epidemiology & population health and of urology at Albert Einstein College of Medicine in New York City.

He said the detection of other oral HPVs (beta and gamma HPVs) were associated with a 3- to 6-fold higher risk of HNSCC after adjustment for smoking, alcohol, and HPV16. The study was carried out with 96 650 participants from 2 large study groups (The American Cancer Society Cancer Prevention Study II Nutrition Cohort and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial).

All subjects were cancer-free at baseline and had available mouthwash samples. The researchers identified 132 cases of HNSCC during an average follow-up of almost 4 years. Among these 132 cases, 103 were men and the average age at baseline was 66.5 years. The study included 396 healthy individuals (3 for every case of HNSCC).

RELATED: HPV16+ Patients With Oropharyngeal Squamous Cell Cancer Survive Longer Than HPV- Patients

“We performed this study since we had previously detected an unusually high prevalence of HPV types found on the skin and skin cancers in the oral cavity in addition to HPV16 and other high-risk types. We wished to determine if these types were associated with risk of head and neck cancers. In addition, we wished to determine if HPV detection preceded the diagnosis of head and neck cancers and might serve as a biomarker. Currently there are no good screening tests for the diseases,” said study author Robert Burk, MD, who is a professor of pediatrics at Albert Einstein College of Medicine.

Dr Burk told Cancer Therapy Advisor that this study is the first to demonstrate conclusively that HPV16 detection in the oral cavity precedes the development of oropharyngeal cancers. In addition, the positive associations of beta and gamma HPVs with increased risk of head and neck cancers suggest a broader role for HPVs in its etiology. The authors noted limitations of the study because of its small sample size, which reflected the rarity of HNSCC.