Human papillomavirus-16 infection in advanced oral cavity cancer patients is related to an increased risk of distant metastases and poor survival.
BACKGROUND
Human papillomavirus (HPV) is an oncogenic virus causing oropharyngeal cancers and resulting in a favorable outcome after the treatment. The role of HPV in oral cavity squamous cell carcinoma (OSCC) remains ambiguous.


OBJECTIVE
This study aimed to examine the effect of HPV infection on disease control among patients with OSCC following radical surgery with radiation-based adjuvant therapy.


METHODS
We prospectively followed 173 patients with advanced OSCC (96% were stage III/IV) who had undergone radical surgery and adjuvant therapy between 2004 and 2006. They were followed between surgery and death or up to 60 months. Surgical specimens were examined using a PCR-based HPV blot test. The primary endpoints were the risk of relapse and the time to relapse; the secondary endpoints were disease-free survival, disease-specific survival, and overall survival.


RESULTS
The prevalence of HPV-positive OSCC was 22%; HPV-16 (9%) and HPV-18 (7%) were the genotypes most commonly encountered. Solitary HPV-16 infection was a poor predictor of 5-year distant metastases (hazard ratio, 3.4; 95% confidence interval, 1.4-8.0; P = 0.005), disease-free survival (P = 0.037), disease-specific survival (P = 0.006), and overall survival (P = 0.010), whereas HPV-18 infection had no impact on 5-year outcomes. The rate of 5-year distant metastases was significantly higher in the HPV-16 or level IV/V metastasis group compared with both the extracapsular spread or tumor depth ≥ 11-mm group and patients without risk factors (P<0.001).


CONCLUSIONS
HPV infections in advanced OSCC patients are not uncommon and clinically relevant. Compared with HPV-16-negative advanced OSCC patients, those with a single HPV-16 infection are at higher risk of distant metastases and poor survival despite undergoing radiation-based adjuvant therapy and require a more aggressive adjuvant treatment and a more thorough follow-up.
Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
Li-Ang
LA
Lee
Chung-Guei
CG
Huang
Chun-Ta
CT
Liao
Li-Yu
LY
Lee
Chuen
C
Hsueh
Tse-Ching
TC
Chen
Chien-Yu
CY
Lin
Kang-Hsing
KH
Fan
Hung-Ming
HM
Wang
Shiang-Fu
SF
Huang
I-How
IH
Chen
Chung-Jan
CJ
Kang
Shu-Hang
SH
Ng
Shu-Li
SL
Yang
Kuo-Chien
KC
Tsao
Yu-Liang
YL
Chang
Tzu-Chen
TC
Yen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000401:mortality / Q000473:pathology / Q000821:virology; D003710:Demography; D005260:Female; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000473:pathology* / Q000821:virology; D009062:Mouth Neoplasms / Q000150:complications* / Q000401:mortality / Q000473:pathology / Q000821:virology*; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D030361:Papillomavirus Infections / Q000150:complications* / Q000473:pathology / Q000821:virology*; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate; D013624:Taiwan / Q000453:epidemiology