Background: Smoking, alcohol consumption, and human papillomavirus (HPV) infection are known risk factors for oral squamous cell carcinoma (OSCC) including SCC of oropharynx (SCCOP) and SCC of oral cavity (SCCOC). Researchers have examined each of these risk factors independently, but few have observed the potential risk of their interaction. This study investigated the interactions among these risk factors and risk of OSCC. Methods: Totally 377 patients with newly diagnosed SCCOP and SCCOC and 433 frequency-matched cancer-free controls by age and sex were included. Multivariable logistic regression was performed to calculate ORs and 95% CIs. Results: We found that overall OSCC risk was independently associated with smoking (adjusted OR(aOR), 1.4; 95%CI, 1.0–2.0), alcohol consumption (aOR, 1.6; 95%CI, 1.1–2.2), and HPV16 seropositivity (aOR, 3.3; 95%CI, 2.2–4.9), respectively. Additionally, we found that HPV16 seropositivity increased the risk of overall OSCC in ever-smokers (aOR, 6.8; 95%CI, 3.4–13.4) and ever-drinkers (aOR, 4.8; 95%CI, 2.9–8.0), while HPV16-seronegative ever-smokers and ever-drinkers had less than a twofold increase in risk of overall OSCC (aORs, 1.2; 95%CI, 0.8–1.7 and 1.8; 95%CI, 1.2–2.7, respectively). Furthermore, the increased risk was particularly high for SCCOP in HPV16-seropositive ever-smokers (aOR, 13.0; 95%CI, 6.0–27.7) and in HPV16-seropositive ever-drinkers (aOR, 10.8; 95%CI, 5.8–20.1), while the similar increased risk was not found in SCCOC. Conclusion: These results suggest a strong combined effect of HPV16 exposure, smoking, and alcohol on overall OSCC, which may indicate a strong interaction between HPV16 infection and smoking and alcohol consumption, particularly for SCCOP.

Susceptibility to cancer has been associated with DNA repair capacity, a global reflection of all functional variants, most of which are relatively rare. Among the 1,098 single nucleotide polymorphisms (SNP) identified in the eight core nucleotide excision repair genes, only a few are common nonsynonymous or regulatory SNPs that are potentially functional. We tested the hypothesis that seven selected common nonsynonymous and regulatory variants in the nucleotide excision repair core genes are associated with risk of squamous cell carcinoma of the head and neck (SCCHN) in a hospital-based, case-control study of 829 SCCHN cases and 854 cancer-free controls. Assuming a recessive genetic model, we found that only carriers of the XPC 499Val/Val genotype had a significantly increased SCCHN risk (adjusted odds ratio, 1.65; 95% confidence interval, 1.16-2.36). In analysis of the joint effects, the number of observed risk genotypes was associated with SCCHN risk in a dose-response manner (P for trend = 0.017) and those who carried four or more risk genotypes exhibited a borderline significant 1.23-fold increased SCCHN risk (adjusted odds ratio, 1.23; 95% confidence interval, 0.99-1.53). In the stratified analysis, the dichotomized combined effect of the seven SNPs was slightly more evident among older subjects, women, and laryngeal cancer. These findings suggest that these potentially functional SNPs may collectively contribute to susceptibility to SCCHN. These findings need to be validated in larger, independent studies. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1633–8)

Single-nucleotide polymorphisms (SNPs) of TERT -rs2736098 (C > T) and CLPTM1L -rs401681(C > T) at the 5p15.33 locus are significantly associated with cancer risk as reported in genome-wide association studies (GWAS), but there are no reported studies for squamous cell carcinoma of the head and neck (SCCHN). In a case–control study of 1079 SCCHN cases and 1115 cancer-free controls of non-Hispanic whites who were frequency matched by age and sex, we genotyped for these two SNPs and assessed their associations with SCCHN risk. Compared with the CC genotypes of each polymorphism, the associations of a slightly reduced risk of SCCHN with the variant genotypes of CT + TT of both polymorphisms were approaching statistical significance [Odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.76–1.08 for TERT -rs2736098 and OR = 0.86, 95% CI = 0.71–1.04 for CLPTM1L -rs401681, respectively]. When the two SNPs were combined, the variant genotypes of the two SNPs were significantly associated a moderately reduced risk of SCCHN (OR = 0.82, 95% CI = 0.67–0.99), and the number of variant genotypes was associated with a significantly reduced risk in a dose–response manner ( P = 0.028). Furthermore, the reduced risk was more pronounced in ever smokers, ever drinkers and patients with oropharyngeal cancer. Our results suggested that these two SNPs at the 5p15.33 locus may be associated with a reduced risk of SCCHN, particularly for their combined effect. Although we added additional evidence for the association of the two SNPs with cancer risk as reported in GWAS, additional studies are needed to replicate our findings.

Kyle J. Gu, Guojun Li. J Cancer Prev 2020;25:127-35. https://doi.org/10.15430/JCP.2020.25.3.127