Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Department of Otolaryngology Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
Cancer Epidemiol Biomarkers Prev. 2024 Apr 3;33(4):516-524. doi: 10.1158/1055-9965.EPI-23-1272.
Effective screening for oropharyngeal cancer is lacking. Four oncogenic HPV clearance definitions were explored to understand long-term natural history for persistent oncogenic oral HPV (oncHPV), the precursor of oropharyngeal cancer.
Prospective multicenter cohort of participants living with/at-risk for HIV, with oral rinse and gargle samples collected every 6 to 12 months for up to 10 years and tested for oncHPV. HPV clearance definitions included 1 (clear1), 2 (clear2), 3 (clear3) consecutive negatives, or being negative at last two visits (clearlast).
Median time to clearance of oncHPV exceeded 2 years for conservative definitions (clear3: 2.38, clearlast: 2.43), but not lenient (clear1: 0.68, clear2: 1.15). By clear3, most incident infections cleared at 2, 5, 8 years (55.1%, 75.6%, 79.1%), contrary to prevalent infections (37.1%, 52.5%, 59.5%, respectively). In adjusted analysis, prevalent oncHPV, older age, male sex, and living with HIV were associated with reduced clearance. Of 1,833 subjects screened, 13.8% had prevalent oncHPV and 47.5% of those infections persisted ≥5 years, representing 6.5% of persons screened. Two men with prevalent oral HPV16 developed incident oropharyngeal cancer [IR = 1.62 per 100 person-years; 95% confidence interval (CI), 0.41-6.4]. Many with oral HPV16 persisted ≥5 years (and/or developed HPV-oropharyngeal cancer) among those with 2 (72.2%), ≥2 of first 3 (65.7%), or 3 (80.0%) consecutive positive oHPV16 tests, but not after 1 (39.4%).
In our 10-year study, most incident infections cleared quickly. However, half of prevalent oncHPV persisted ≥5 years, suggesting increased risk with persistent oncHPV at >2 visits.
We identified groups with persistent oncHPV at increased risk of oropharyngeal cancer and contextualized risk levels for those with oral HPV16 infection.
目前缺乏有效的口咽癌筛查方法。本研究旨在探索四种致癌 HPV 清除定义，以了解持续性致癌口腔 HPV（oncHPV）的长期自然史，oncHPV 是口咽癌的前身。
本研究为前瞻性多中心队列研究，纳入了 HIV 感染者或 HIV 高危人群，每 6-12 个月采集一次口腔冲洗和漱口样本，最长随访 10 年，并检测 oncHPV。HPV 清除定义包括 1（clear1）、2（clear2）、3（clear3）次连续阴性，或最后两次检测均为阴性（clearlast）。
对于保守的清除定义（clear3：2.38，clearlast：2.43），oncHPV 的中位清除时间超过 2 年，但对于宽松的清除定义（clear1：0.68，clear2：1.15）则不然。到 2、5、8 年时，通过 clear3 清除的新发感染分别为 55.1%、75.6%和 79.1%，而既往感染的清除率分别为 37.1%、52.5%和 59.5%。多因素分析显示，既往 oncHPV 感染、年龄较大、男性和 HIV 感染与清除率降低相关。在 1833 名筛查对象中，13.8%有既往 oncHPV 感染，其中 47.5%的感染持续≥5 年，占筛查人数的 6.5%。两名患有既往口腔 HPV16 感染的男性发生了新发口咽癌[发病率为 1.62/100 人年；95%置信区间（CI）为 0.41-6.4]。在那些连续 3 次（80.0%）或至少 2 次（65.7%）、≥2 次（65.7%）阳性的口腔 HPV16 检测结果为阳性的人中，有许多人持续≥5 年（或发展为 HPV 口咽癌），但在只有 1 次阳性（39.4%）的人中没有。
在我们的 10 年研究中，大多数新发感染很快被清除。然而，一半的既往 oncHPV 持续存在≥5 年，提示持续存在 oncHPV 与≥2 次就诊时的口咽癌风险增加相关。
本研究确定了持续存在 oncHPV 风险增加的人群，对口咽癌高危人群进行了风险分层，并对口咽癌高危人群进行了风险分层。
