Rising incidence of HPV positive oropharyngeal cancer in Taiwan between 1999 and 2014 where betel nut chewing is common

Abstract

Background: The incidence of human papillomavirus (HPV) positive oropharyngeal cancer (OPC) is rising but HPV negative OPC is decreasing in Western countries. In Taiwan, the incidence of HPV negative OPC is common but the incidence of HPV positive OPC remains unknown. The objective of this study is to estimate the incidence trend and the survival of HPV positive OPC in Taiwan.

Methods: Between 1999 and 2014, primary tumor tissues from 425 incident OPCs were obtained from 5 medical centers in Taiwan. 408 OPCs were evaluated by the EasyChip HPV genotyping (King-Car, I-Lan, Taiwan) and 369 OPCs by p16 staining. The clinical data were retrospectively obtained from the medical records.

Results: In our study, 29% of OPCs were HPV positive. The percentage of HPV positive OPC was stable from 1999 to 2014 (25% (1999-2002), 30% (2003-2006), 30% (2007-2010), 29% (2011-2014)). The estimated crude incidence rate of HPV positive OPC increased significantly from 0.62 (1999-2002), 1.06 (2003-2006), 1.52 (2007-2010) to 1.74 (2011-2014) per 100,000 person-year. The sensitivity and specificity of p16 staining for positive HPV infection were 92% and 91%, respectively. The 5-year overall survival rates for patients with HPV positive OPC and with HPV negative OPC were 67.8% and 49.0%, respectively (HR = 0.52 (0.35-0.76), p = 0.0005). Patients with HPV positive OPC but no betel nut/cigarette exposure had the best overall survival (5-year: 88.2%, p < 0.0001). Patients with HPV negative OPC and betel nut/cigarette exposure had the worst overall survival (5-year: 46.6%, p < 0.0001). Patients with HPV positive OPC but also with betel nut/cigarette exposure had poorer 5-year overall survival (48.3%, p < 0.01).

Conclusion: The incidence of HPV positive OPC is increasing along with HPV negative OPC, which leads to stably low percentage of HPV positive OPC in Taiwan. HPV positive OPC may become an important head and neck cancer when the incidence of HPV negative OPC declines in the near future. P16 is a useful surrogate marker for HPV infection in OPC and a good prognostic indicator for treatment outcome of OPC. Patients with HPV positive OPC but no betel nut/cigarette exposure has an excellent prognosis. Betel nut/cigarette exposure significantly worsens the prognosis of HPV positive OPC.

Keywords: Betel nut; Human papillomavirus; Incidence; Oropharyngeal cancer; p16.

Fig. 1

Prevalence of HPV positive OPC in 408 OPCs across four calendar periods (1999 to 2002, 2003 to 2006, 2007 to 2010, and 2010 to 2014) determined by HPV PCR

Fig. 2

a Estimated crude incidence rates of HPV positive OPC across four calendar periods (1999 to 2002, 2003 to 2006, 2007 to 2010, and 2010 to 2014) determined by HPV PCR. Blue line represents the average crude incidence rate of all OPC including man and woman during the 4 calendar years in Taiwan. Red line represents the estimated average crude incidence rate of HPV positive OPC including man and woman during the 4 calendar years in Taiwan. b Estimated crude incidence rates of male HPV positive OPC across four calendar periods (1999 to 2002, 2003 to 2006, 2007 to 2010, and 2010 to 2014) determined by HPV PCR. The blue line represents the average crude incidence rate of all male OPC during the 4 calendar years in Taiwan. The red line represents the estimated average crude incidence rate of male HPV positive OPC during the 4 calendar years in Taiwan

Fig. 3

HPV subtype distribution of 119 HPV positive OPCs by HPV PCR genotyping

Fig. 4

Overall survival curves of the OPC patients stratified by HPV PCR testing (a) and p16 IHC staining (b) in Taiwan. Impact of betel nut/cigarette (BC) exposure on the overall survival of HPV positive OPC patients (c)