medwireNews: Infection with human papillomavirus type 16 (HPV16) has an important role in the etiology of oropharyngeal cancers, results from a large case-control study indicate.
The research also identified minor roles for HPV18 in oropharyngeal cancer and HPV6 in laryngeal cancer, highlighting the importance of HPV serology when investigating tumors of the upper aero-digestive tract (UADT).
Paul Brennan (International Agency for Research on Cancer, Lyon, France) and team analyzed serum and tissue samples from 1496 people with UADT cancers and 1425 healthy control individuals matched for age, gender, and area of residence.
The patients had been participating in the ARCAGE (Alcohol-Related Cancers and Genetic Susceptibility in Europe) study, which was conducted in 10 European countries between 2002 and 2005.
Serum samples were tested for a panel of 27 markers of HPV infection, including high-risk and low-risk types as well as antibodies to cutaneous HPV types, while tissue samples were analyzed for HPV DNA.
Writing in the Journal of the National Cancer Institute, Brennan's team reports that, as expected, smoking and alcohol consumption were strongly associated with UADT cancer risk.
HPV16 L1 seropositivity was associated with increased risk for oral cavity and oropharyngeal cancer, at odds ratios (ORs) of 1.94 and 8.60, respectively. These risks were higher in never-smokers than in current or former smokers.
Anti-HPV16 E6 antibodies were present in 30.2% of patients with oropharyngeal cancer but in just 0.8% of healthy controls, giving an 18-fold increased UADT cancer risk (OR=18.44). This association was consistent irrespective of gender and smoking status.
Anti-HPV16 E7 antibodies were also associated with UADT cancer (OR=2.86), with the risk being higher among never and former smokers, compared with current smokers.
Combined seropositivity to HPV16 E6 and E7 was very rare among controls and was associated with increased risk for UADT cancer at all sites and with a more than 800-fold increased risk for oropharyngeal cancer.
Finally, there were HPV16-independent associations between HPV18 and oropharyngeal cancer (OR=8.14) and between HPV6 and laryngeal cancer (OR=3.25).
The researchers note that while the majority of HPV16 infections in the UADT appear to be inactive, at least 30% of oropharyngeal cancers are HPV16-related.
"HPV16 E6 antibodies are promising markers to identify HPV16 DNA-positive/p16-overexpressing tumors," they write.
"Larger focused studies will be required to clarify the appropriate algorithm to accurately identify HPV-related UADT cancers. Given the increasing proportion of oropharyngeal cancers in Europe, the value of HPV16 E6 serology warrants further investigation."
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