title: Increasing rates of low-risk human papillomavirus infections in patients with oral cavity squamous cell carcinoma: association with clinical outcomes.
abstract: BACKGROUND
  Although human papillomavirus (HPV) infections have been causally linked to oral cavity squamous cell carcinoma (OSCC), the potential role of low-risk HPV (LR-HPV) types in the pathogenesis of this malignancy remains unclear.
  
  
  OBJECTIVE
  We sought to investigate the distribution of HPV genotypes and their prognostic significance in OSCC patients treated by radical surgery, either with or without adjuvant therapy.
  
  
  METHODS
  We studied two non-overlapping OSCC cohorts for the periods 2005-2006 (2005 cohort, n = 204) and 2010-2011 (2010 cohort, n = 206). Paraffin-embedded tissue blocks were collected, and the HPV genotype was determined using PCR plus HPV blot tests. The primary study endpoint was the prevalence of HPV genotypes. The secondary endpoints were the 2-year therapeutic outcomes.
  
  
  RESULTS
  The overall prevalence of HPV infections did not differ significantly in the two study cohorts. However, the prevalence of LR-HPV was significantly higher in the 2010 cohort than in the 2005 cohort (p = 0.002). The overall prevalence of HPV infections was not significantly associated with the 2-year outcomes. However, multivariate analysis demonstrated that LR-HPV infection was a predictor of poor 2-year disease-free survival (p = 0.036, hazard ratio [HR] = 3.1), disease-specific survival (p = 0.014, HR = 3.8), and overall survival (p = 0.016, HR = 3.2) in the subgroups of OSCC patients with poor differentiation, pN2 lymph node metastases, or extracapsular spread (n = 150).
  
  
  CONCLUSIONS
  LR-HPV infections may have an important role in determining the clinical outcomes of certain OSCC patients bearing specific risk factors.
authors.affiliation: Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, ROC.
authors.forename: Li-Ang
authors.initials: LA
authors.lastname: Lee
authors.forename: Chung-Guei
authors.initials: CG
authors.lastname: Huang
authors.forename: Kuo-Chien
authors.initials: KC
authors.lastname: Tsao
authors.forename: Chun-Ta
authors.initials: CT
authors.lastname: Liao
authors.forename: Chung-Jan
authors.initials: CJ
authors.lastname: Kang
authors.forename: Kei-Ping
authors.initials: KP
authors.lastname: Chang
authors.forename: Shiang-Fu
authors.initials: SF
authors.lastname: Huang
authors.forename: I-How
authors.initials: IH
authors.lastname: Chen
authors.forename: Tuan-Jen
authors.initials: TJ
authors.lastname: Fang
authors.forename: Hsueh-Yu
authors.initials: HY
authors.lastname: Li
authors.forename: Shu-Li
authors.initials: SL
authors.lastname: Yang
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Lee
authors.forename: Chuen
authors.initials: C
authors.lastname: Hsueh
authors.forename: Tse-Ching
authors.initials: TC
authors.lastname: Chen
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Kang-Hsing
authors.initials: KH
authors.lastname: Fan
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Wang
authors.forename: Shu-Hang
authors.initials: SH
authors.lastname: Ng
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Chang
authors.forename: Chyong-Huey
authors.initials: CH
authors.lastname: Lai
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Shih
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000473:pathology / Q000821:virology*; D009062:Mouth Neoplasms / Q000473:pathology / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications* / Q000473:pathology / Q000821:virology; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors