Sexual transmission of human papillomavirus, particularly HPV16, has been associated with an increasing incidence of oropharyngeal squamous cell carcinoma (OPC). Telomere shortening results in chromosomal instability, subsequently leading to cancer development. Given that HPV16 can affect telomerase activity and telomere length (TL), we conjectured that TL in peripheral blood lymphocytes (PBLs) may affect the risk of HPV16-associated OPC and tumor HPV16 status in patients. TL in PBLs and HPV16 serological status were measured in peripheral blood samples in 188 patients with OPC, 137 patients with oral cavity cancer (OCC) and 335 controls of non-Hispanic whites. Tumor HPV status was determined in 349 OPC cases. Odds ratios and 95% confidence intervals were calculated in univariate and multivariable logistic regression models. Overall, compared with long TL, short TL was associated significantly with a moderately increased risk of OPC but no increased risk of OCC. When we stratified the data by HPV16 serological status, using long TL and HPV16 seronegativity as the reference group, we found that the risk associated with HPV16 seropositivity was higher among OPC patients with short TL. Notably, such risk was particularly pronounced in never smokers, never drinkers and those >50 years of age. Furthermore, short TL was also associated significantly with tumor HPV-positive OPC. Together, our findings suggest that TL in PBLs may be associated with higher risk of HPV16-associated OPC and tumor HPV16 status, particularly in certain patient subgroups. Larger studies are needed to validate these findings.
PMID: 23928994

Telomere length in peripheral blood lymphocytes contributes to the development of HPV-associated oropharyngeal carcinoma.