Abstract
p53 and p73 interact with human papillomavirus (HPV) E6 and E7 oncoproteins. The interplay between p53 and p73 and HPV16 may lead to deregulation of cell cycle and apoptosis, through which inflammation/immune responses control the HPV clearance and escape of immune surveillance, and subsequently contribute to tumor HPV16 status. In this case-case comparison study, HPV16 status in tumor specimens was analyzed and p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms were genotyped using genomic DNA from blood of 309 oropharyngeal cancer patients. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated in univariate and multivariable logistic regression models to examine the association. The results from this study showed both p53 variant genotypes (Arg/Pro+Pro/Pro) and p73 variant genotypes (GC/AT+AT/AT) were significantly associated with HPV16-positive tumor in oropharyngeal cancer patients (OR, 1.9, 95% CI, 1.1–3.3 and OR, 2.1, 95% CI, 1.2–3.8, respectively), while the combined variant genotypes (p53 Pro carriers and p73 AT carriers) exhibited a significantly greater association with HPV16-positive tumor (OR, 3.2, 95% CI, 1.4–7.4), compared with combined wild-type genotypes (p53 Arg/Arg and p73 GC/GC), and the association was in a statistically significant dose-effect relationship (p = 0.001). Moreover, such association was more pronounced among several subgroups. These findings suggest that variant genotypes of p53 and p73 genes may be individually, or more likely jointly, associated with tumor HPV16-positive oropharyngeal cancer patients, particularly in never smokers. Identification of such susceptible biomarkers would greatly influence on individualized treatment for an improved prognosis.
Highlights
Squamous cell carcinoma of the head and neck (SCCHN) typically presents in advanced stages and is associated with poor survival and high recurrence and second primary tumor rates [1]
We and others have previously assessed associations of these two polymorphisms with human papillomavirus (HPV)-associated SCCHN or their subgroups in several studies [31,32,33,34,35], while these studies categorized HPV16 status of study patients based on serology or included mixed cancer sites due to the unavailability of tumor status in our previous studies [31,32,34,35]
The data from this study suggest that variant genotypes of each polymorphism may individually, and more likely jointly, influence on tumor HPV16 status in oropharyngeal cancer and could be potentially susceptible markers for the tumor HPV16-positive patients
Summary
Squamous cell carcinoma of the head and neck (SCCHN) typically presents in advanced stages and is associated with poor survival and high recurrence and second primary tumor rates [1]. HPV tumor positivity confers a favorable outcome, independent of other significant confounding factors including stage, treatment, smoking, etc, HPV-positive cancers are more likely to have a later stage, nodal involvement and advanced grade compared to HPV-negative cancers [12]. These facts may promote consideration for a new staging system for oropharyngeal cancer, stratified by HPV status. Identification of new biomarkers for tumor HPV status detection (e.g., HPV DNA in tumors) may help ensure appropriate therapy for a better clinical outcome
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