Authors' Affiliations: Departments of Head and Neck Surgery, and Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Cancer Res. 2013 Oct 1;73(19):5996-6003. doi: 10.1158/0008-5472.CAN-13-0881. Epub 2013 Aug 8.
Sexual transmission of human papillomavirus (HPV), 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, we conjectured that telomere length in peripheral blood lymphocytes (PBL) might affect the risk of HPV16-associated OPC and tumor HPV16 status in patients. Telomere length in PBLs and HPV16 serologic 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. ORs and 95% confidence intervals were calculated in univariate and multivariable logistic regression models. Overall, as compared with the long telomere length, short telomere length was significantly associated with a moderately increased risk of OPC but not with increased risk of OCC. When we stratified the data by HPV16 serologic status, using long telomere length and HPV16 seronegativity as the reference group, we found that the risk associated with HPV16 seropositivity was higher among patients with OPC with short telomere length. Notably, such risk was particularly pronounced in never smokers, never drinkers, and those more than 50 years of age. Furthermore, short telomere length was also associated significantly with tumor HPV-positive OPC. Together, our findings suggest that telomere length 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.
人乳头瘤病毒（HPV）的性传播，尤其是 HPV16，与口咽鳞状细胞癌（OPC）的发病率增加有关。端粒缩短会导致染色体不稳定，进而导致癌症的发展。鉴于 HPV16 可能影响端粒酶活性和端粒长度，我们推测外周血淋巴细胞（PBL）中的端粒长度可能会影响 HPV16 相关 OPC 的风险以及患者肿瘤中 HPV16 的状态。我们在 188 名 OPC 患者、137 名口腔癌（OCC）患者和 335 名非西班牙裔白人对照组的外周血样本中测量了 PBL 中端粒长度和 HPV16 血清学状态。在 349 例 OPC 病例中确定了肿瘤 HPV 状态。我们在单变量和多变量逻辑回归模型中计算了比值比（OR）和 95%置信区间（CI）。总的来说，与长端粒长度相比，短端粒长度与 OPC 的中度风险增加显著相关，但与 OCC 的风险增加无关。当我们根据 HPV16 血清学状态对数据进行分层时，以长端粒长度和 HPV16 血清阴性作为参考组，我们发现 HPV16 血清阳性与短端粒长度 OPC 患者的风险相关更高。值得注意的是，这种风险在从不吸烟者、不饮酒者和年龄超过 50 岁的人群中更为明显。此外，短端粒长度也与肿瘤 HPV 阳性 OPC 显著相关。总之，我们的研究结果表明，PBL 中的端粒长度可能与 HPV16 相关的 OPC 和肿瘤 HPV16 状态的更高风险相关，尤其是在某些特定的患者亚组中。需要更大规模的研究来验证这些发现。
