Association of p73 G4C14‐to‐A4T14 polymorphism with human papillomavirus type 16 status in squamous cell carcinoma of the head and neck in non‐Hispanic whites

Abstract

BACKGROUND:The tumor protein p73 interacts with the human papillomavirus type 16 (HPV‐16) oncoproteins E6 and E7, and p73 variation may modify the interaction between p73 protein and HPV‐16 oncogenic proteins and contribute to cellular malignant transformation.METHODS:In this case‐case comparison study, the authors analyzed HPV‐16 status in tumor specimens and genotyped the p73 G4C14‐to‐A4T14 polymorphism using genomic DNA from blood of 202 non‐Hispanic white patients with squamous cell carcinoma of the head and neck (SCCHN). Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated in univariate and multivariable logistic regression models to examine the association between the p73 polymorphism and HPV‐16 status in SCCHN.RESULTS:Compared with the p73 GC/GC genotype, the AT/AT and combined GC/AT + AT/AT variant genotypes were associated significantly with HPV‐16‐positive tumor status among patients with SCCHN (adjusted OR, 5.32; 95% CI, 1.32‐21.4; adjusted OR, 1.91; 95% CI, 1.03‐3.53, respectively). There was a significant dose‐effect relation between the AT allele and HPV‐16‐positive tumor status in patients with SCCHN (trend test: P = .014). Moreover, the stratified analyses indicated that the association between HPV‐16‐positive tumor status and the combined p73 GC/AT + AT/AT genotypes was more pronounced among several subgroups of patients who were older, men, ever drinkers, and those with oropharyngeal cancer.CONCLUSIONS:The p73 polymorphism was associated with HPV‐16 status in SCCHN and may serve as a marker of positive HPV‐16 tumor status in patients with SCCHN, particularly those with oropharyngeal cancer. Cancer 2009. © 2009 American Cancer Society.

Socioeconomic characteristics of patients with oropharyngeal carcinoma according to tumor HPV status, patient smoking status, and sexual behavior

“…We extracted DNA using a tissue DNA extraction kit (Qiagen Inc., Valencia, CA) and tested this DNA for the presence of HPV16 DNA using a type-specific PCR-based assay with modification for the E6 and E7 regions [15]. Samples were run in triplicate with positive and negative controls and β-actin as a quality control.…”

A TGF‐β1 genetic variant at the miRNA187 binding site significantly modifies risk of HPV16‐associated oropharyngeal cancer

“…The patients had been recruited at The University of Texas MD Anderson Cancer Center as part of an ongoing molecular epidemiologic study, in which the patient eligibility criteria have been described previously 16, 17 . During that same period, 335 controls were recruited by the Kelsey-Seybold Foundation from a pool of healthy subjects, which included residents of metropolitan Houston, and by MD Anderson Cancer Center from a pool of healthy visitors who had accompanied cancer patients but were genetically unrelated to the patients.…”

“…For serologic testing, we generated HPV16 L1 virus-like particles from insect cells infected with recombinant baculovirus to test for antibodies against the HPV16 L1 capsid protein in the plasma; this was done with the use of a standard enzyme-linked immunosorbent assay (ELISA), as described previously 17 . Two groups of control sera, one known to be positive and the other known to be negative, were tested in parallel with the study samples in duplicate on each plate.…”

“…The samples of DNA were extracted from paraffin-embedded tumor tissues of patients and determined for the presence of HPV16 using polymerase chain reaction and in situ hybridization methods described in our previous studies 15, 17 . For some patients, tumor HPV16 status was determined by in situ hybridization and p16 immunohistochemical analysis from HPV data in the patient’s clinical records, since the pathology laboratory at MD Anderson had begun classifying all OPSCC specimens as a standard clinical practice.…”

Genetic variants in microRNA‐binding sites of DNA repair genes as predictors of recurrence in patients with squamous cell carcinoma of the oropharynx

“…Tumor HPV16 status was determined from paraffin-embedded tissue biopsy specimens or surgical specimens, when available. DNA was extracted from tissue specimens and analyzed for HPV16 using PCR and confirmed by ISH, as described previously 18 . For quality control, 10% of randomly selected samples were re-assayed for tumor HPV16 status; the re-run results reached a 100% concordance with the original results.…”