Human Papillomavirus Infections and Upper Aero-Digestive Tract Cancers: The ARCAGE Study
Human Papillomavirus Infections and Upper Aero-Digestive Tract Cancers: The ARCAGE Study
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DOI：
10.1093/jnci/djt053
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发表时间：
2013-04-01
影响因子：
10.3
通讯作者：
Brennan, Paul
中科院分区：
文献类型：
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作者：
Anantharaman, Devasena;Gheit, Tarik;Brennan, Paul
人乳头瘤病毒（HPV）与上呼吸消化道（UADT）癌的发生密切相关，通过Logistic回归分析，对1496例UADT癌病例和1425例对照组进行HPV抗体检测，并对潜在混杂因素进行校正，以估计OR值。HPV感染的血清学和肿瘤标志物之间的一致性，包括HPV DNA和p16表达的存在，在一个肿瘤子集中进行了检查，HPV 16 L1血清学阳性与口腔和口咽癌的风险增加相关（OR 1.94，95%置信区间[CI] 1.03 - 3.65; OR 8.60，95% CI 5.21 - 14.20）。HPV 16 E6抗体在口咽部病例组中的阳性率为30.2%，对照组仅为0.8%（OR 132.0，95%CI 65.29 ~ 266.86）。HPV 16 E6和E7的联合血清阳性很罕见（1425例对照受试者中的1例）。在HPV 16 E6血清学和HPV相关癌症的相应存在之间观察到67%的一致性：6个HPV DNA阳性/p16过表达肿瘤中有4个是HPV 16 E6抗体阳性。HPV 16感染与口咽癌和喉癌的关系分别为HPV 18 E6血清阳性OR 8.14，95%CI 2.21 ~ 29.99和HPV 6 E7血清阳性OR 3.25，95%CI 1.46 ~ 7.24，证实了HPV 16感染在口咽癌中的重要作用。HPV 16 E6抗体与HPV 16相关的口咽癌密切相关。需要继续努力将HPV血清学和p16染色作为与HPV 16相关口咽肿瘤的病因学和自然史相关的生物标志物。这些结果也支持HPV 18在口咽癌和HPV 6在喉癌中的边缘作用。
Human papillomavirus (HPV) is causally implicated in a subset of cancers of the upper aero-digestive tract (UADT).Associations between type-specific HPV antibodies were examined among 1496 UADT cancer case subjects and 1425 control subjects by estimating odds ratios (ORs) in logistic regression analyses adjusted for potential confounders. The agreement between serology and tumor markers of HPV infection, including presence of HPV DNA and p16 expression, were examined in a subset of tumors.HPV16 L1 seropositivity was associated with increased risk of oral cavity and oropharyngeal cancer (OR 1.94, 95% confidence interval [CI] 1.03 to 3.65; OR 8.60, 95% CI 5.21 to 14.20, respectively). HPV16 E6 antibodies were present in 30.2% of oropharyngeal case subjects and only 0.8% of control subjects (OR 132.0, 95% CI 65.29 to 266.86). Combined seropositivity to HPV16 E6 and E7 was rare (n 1 of 1425 control subjects). An agreement of 67% was observed between HPV16 E6 serology and the corresponding presence of an HPV-related cancer: four of six HPV DNA-positive/p16-overexpressing tumors were HPV16 E6 antibody positive. An HPV16 independent association was observed for HPV18 and oropharyngeal cancer (OR 8.14, 95% CI 2.21 to 29.99 for HPV18 E6 seropositivity) and HPV6 and laryngeal cancer (OR 3.25, 95% CI 1.46 to 7.24 for HPV6 E7 seropositivity).These results confirm an important role for HPV16 infection in oropharyngeal cancer. HPV16 E6 antibodies are strongly associated with HPV16-related oropharyngeal cancers. Continuing efforts are needed to consider both HPV serology and p16 staining as biomarkers relevant to the etiology and natural history of HPV16-related oropharyngeal tumors. These results also support a marginal role for HPV18 in oropharyngeal cancer and HPV6 in laryngeal cancer.