Background: The incidence of HPV positive oropharyngeal cancer is rising, but that of HPV negative cancer is decreasing in the most Western countries in the past decades. In Taiwan, the incidence of HPV negative head and neck cancer is still rapidly increasing because betel nut chewing is still common. The object of this study is to evaluate the incidence trend and the survival of HPV positive oropharyngeal cancer in Taiwan where betel nut chewing is the major risk factor for head and neck cancer.
Methods: Between 1999 and 2014, the FFPE surgical specimens of 425 incident oropharyngeal cancers without other head and neck cancers were obtained from 5 hospitals in Taiwan (one hospital in Northern Taiwan, two in Middle Taiwan, one in Southern Taiwan and one in the Eastern Taiwan). Among them, 369 cancers were successfully evaluated by p16 immunostaining (CINtec Histology Kit, Roche mtm laboratories) and 408 cancers were evaluated by the EasyChip HPV genotyping array (King-Car, I-Lan, Taiwan) and gel electrophoresis. Positive p16 was defined as strong and diffuse nuclear and cytoplasmic staining in 70% or more of the tumor cells. The clinical data were retrospectively obtained from the medical records. The survival was calculated to Dec 31, 2014.
Results:: Of all oropharyngeal cancers, p16 positive cancers were 31% and HPV positive cancers were 29%. The percentages of p16 positive and HPV positive cancers were not significantly changed from 1999 to 2014 (24%, 34%, 33%, 28% for positive p16; 25%, 30%,30%, 29% for positive HPV PCR in the periods of 1999-2002, 2003-2006,2007-2010, and 2011-2014). But the incidence of HPV positive oropharyngeal cancer is significantly rising from 0.59 to 1.2 per 100,000, along with HPV negative oropharyngeal cancer from 1.76 to 2.95 per 100,000 in the past 16 years. Among HPV positive cancers, 70% were HPV 16 and 12% were HPV 58, which were compatible with HPV data in cervical cancer in Taiwan. The association between p16 and HPV was very strong (p<0.001). The overall survivals of HPV positive cancers and p16 positive cancers were significantly better than those of HPV negative cancers and p16 negative cancers (HR=0.52 (0.35-0.76), p<0.001; HR=0.39 (0.26-0.59), p<0.001, respectively). The patients with positive HPV but no exposure to betel nut or tobacco had the best prognosis; those with positive HPV and betel nut or tobacco had worse prognosis and those with negative HPV, but positive exposure to betel nut or tobacco had the worst prognosis.
Conclusion:: Despite the percentage of HPV positive oropharyngeal cancer is not significantly increasing, the incidence of HPV positive oropharyngeal cancer is significantly rising by one fold in Taiwan in the past 16 years. Exposure to betel nut worsens the prognosis of HPV positive oropharyngeal cancer.