title: Association of genetic variants with tumor HPV16 status and survival in squamous cell carcinoma of the oropharynx.
abstract: OBJECTIVE
  Genetic polymorphisms of genes in cell cycle, apoptosis, and inflammation/immune response pathways may control the mechanisms of HPV clearance and HPV escape of immune surveillance and thus may affect both tumor HPV16 status and possibly related outcomes of squamous cell carcinoma of the oropharynx (SCCOP) patients.
  
  
  METHODS
  We determined tumor HPV16 status and genotyped selected polymorphisms in key genes involved in cell cycle, apoptosis, and inflammation/immune response pathways in 401 incident SCCOP patients. Unconditional logistic regression models, Kaplan-Meier analysis, and Cox proportional hazards regression were used to evaluate associations and survival.
  
  
  RESULTS
  Compared to the corresponding common homozygous genotypes, the variant genotypes of genes in cell cycle (p53, p73, MDM2, p16), apoptosis (CASP8, and Fas), and inflammation/immune response pathways (IL1β and IL10) were significantly associated with HPV16-positive tumors among SCCOP patients. In HPV16-positive SCCOP patients only, compared to those with the corresponding common homozygous genotypes, patients with variant genotypes of p53 (119G>C), MDM2 (309T>G), p16 (580C>T), Fas (1377G>A), and IL1β (14T>C) had significantly better overall survival, and approximately 40-70% reduced or 5-fold increased risk of overall death, respectively, after adjustment for important prognostic confounders. Moreover, the combined adverse genotypes of 5 variants were also significantly associated with reduced risk of overall death of HPV16-positive SCCOP.
  
  
  CONCLUSIONS
  These results suggest that genetic polymorphisms in likely functional regions of the genes in these pathways may individually or, more likely, jointly affect individual susceptibility to HPV16 tumor status and constitute the confounding effect on HPV16-related clinical outcomes. Validation of our findings is warranted.
authors.affiliation: Department of Otorhinolaryngology Head & Neck Surgery, China Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Otolaryngology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Yuncheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Beijing Institute of Otolaryngology, Beijing 100730, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. Electronic address: zheng_hl2004@163.com.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: gli@mdanderson.org.
authors.forename: Guojun
authors.initials: G
authors.lastname: Li
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000821:virology*; D005260:Female; D014644:Genetic Variation; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000821:virology*
keywords: Genetic variants; HPV16 status; Squamous cell carcinoma of the oropharynx; Survival; Susceptibility biomarkers