D'Souza Gypsyamber, Clemens Gwendolyn, Strickler Howard D, Wiley Dorothy J, Troy Tanya, Struijk Linda, Gillison Maura, Fakhry Carole
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Hospital, Baltimore, MD, USA.
JNCI Cancer Spectr. 2020 Jun 5;4(5):pkaa047. doi: 10.1093/jncics/pkaa047. eCollection 2020 Oct.
Human papillomavirus-related oropharyngeal cancer (HPV-OPC) incidence is increasing, but the natural history of the precursor-oral HPV-has not been well described.
This observational cohort study of people living with HIV and at-risk HIV uninfected people evaluated participants semiannually using 30-second oral rinse and gargle specimens over 7 years. Initially, 447 participants were followed for 4 years as part of the Persistent Oral Papillomavirus Study, and a subset of 128 who showed persistent infections at the last Persistent Oral Papillomavirus Study visit had an additional visit, as part of the Men and Women Understanding Throat HPV Study, on average 2.5 years later. Extracted DNA from oral rinse and gargle specimens was amplified using polymerase chain reaction and type specification of 13 oncogenic HPV types. Risk factors for oncogenic oral HPV clearance were evaluated using Cox models.
The majority of oncogenic oral HPV infections cleared quickly, with a median time to clearance of 1.4 years (interquartile range = 0.5-3.9 years). After 7 years of follow-up, 97% of incident and 71% of prevalent infections had cleared. Lower HPV-16 viral load was statistically significantly associated with clearance (per 10-fold decrease in copy number: adjusted hazard ratio [aHR] = 2.51, 95% confidence interval [CI] = 1.20 to 5.26; = .01). Adjusted analyses showed that oncogenic oral HPV clearance was lower among prevalent than incident-detected infections (aHR = 0.44, 95% CI = 0.35 to 0.55), among men than women (aHR = 0.74, 95% CI = 0.60 to 0.91), for older participants (aHR per 10 years increasing age = 0.81, 95% CI = 0.74 to 0.89), and among people living with HIV (aHR = 0.76, 95% CI = 0.60 to 0.95). One participant who had oral HPV-16 consistently detected at 10 study visits over 4.5 years was subsequently diagnosed with HPV-OPC.
This prospective study of oncogenic oral HPV infection is the longest and largest quantification of oral HPV-16 infections to date.
人乳头瘤病毒相关口咽癌（HPV-OPC）的发病率正在上升，但前驱性口腔HPV的自然史尚未得到充分描述。
这项针对HIV感染者和有HIV感染风险的未感染者的观察性队列研究，在7年时间里每半年使用30秒口腔冲洗和漱口标本对参与者进行评估。最初，447名参与者作为持续性口腔乳头瘤病毒研究的一部分被随访了4年，其中128名在持续性口腔乳头瘤病毒研究最后一次访视时显示持续感染的参与者，作为男性和女性了解咽喉HPV研究的一部分，平均在2.5年后又进行了一次访视。从口腔冲洗和漱口标本中提取的DNA使用聚合酶链反应进行扩增，并对13种致癌性HPV类型进行分型。使用Cox模型评估致癌性口腔HPV清除的危险因素。
大多数致癌性口腔HPV感染迅速清除，清除的中位时间为1.4年（四分位间距=0.5-3.9年）。经过7年的随访，97%的新发感染和71%的既往感染已清除。较低的HPV-16病毒载量与清除在统计学上显著相关（每拷贝数下降10倍：调整后的风险比[aHR]=2.51，95%置信区间[CI]=1.20至5.26；P=.01）。调整后的分析显示，既往感染中致癌性口腔HPV的清除率低于新发感染（aHR=0.44，95%CI=0.35至0.55），男性低于女性（aHR=0.74，95%CI=0.60至0.91），年龄较大的参与者（每增加10岁的aHR=0.81，95%CI=0.74至0.89），以及HIV感染者（aHR=0.76，95%CI=0.60至0.95）。一名在4.5年的10次研究访视中持续检测到口腔HPV-16的参与者随后被诊断为HPV-OPC。
这项关于致癌性口腔HPV感染的前瞻性研究是迄今为止对口腔HPV-16感染进行的时间最长、规模最大的定量研究。
