HPV 16、18 或 45 与细胞学非典型腺细胞（AGC）的联合发现表明原位和浸润性宫颈腺癌的风险大大增加。
The combined finding of HPV 16, 18, or 45 and cytologic Atypical Glandular Cells (AGC) indicates a greatly elevated risk of in situ and invasive cervical adenocarcinoma.
机构信息
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.
出版信息
Gynecol Oncol. 2023 Jul;174:253-261. doi: 10.1016/j.ygyno.2023.05.011. Epub 2023 May 25.
BACKGROUND
Cervical screening has not effectively controlled cervical adenocarcinoma (AC). Human papillomavirus (HPV) testing is recommended for cervical screening but the optimal management of HPV-positive individuals to prevent AC remains a question. Cytology and HPV typing are two triage options to predict the risk of AC. We combined two potential biomarkers (atypical glandular cell, AGC, cytology and HPV-types 16, 18, or 45) to assess their joint effect on detecting AC.
METHODS
Kaiser Permanente Northern California (KPNC) used triennial co-testing with cytology and HPV testing (positive/negative) for routine cervical screening between 2003 and 2020. HPV typing of a sample of residual HPV test specimens was performed on a separate cohort selected from KPNC (Persistence and Progression, PaP, cohort). We compared risk of prevalent and incident histologic AC/AIS (adenocarcinoma in situ) associated with preceding combinations of cytologic results and HPV typing. Risk of squamous cell cancer (SCC)/cervical intraepithelial neoplasia grade 3 (CIN3) (SCC/CIN3) was also included for comparison.
RESULTS
Among HPV-positive individuals in PaP cohort, 99% of prevalent AC and 96% of AIS were linked to HPV-types 16, 18, or 45 (denoted HPV 16/18/45). Although rare (0.09% of screening population), the concurrent detection of HPV 16/18/45 with AGC cytology predicted a highly elevated relative risk of underlying histologic AC/AIS; the absolute risk of diagnosing AC/AIS was 12% and odds ratio (OR) was 1341 (95%CI:495-3630) compared to patients with other high-risk HPV types and normal cytology. Cumulatively (allowing non-concurrent results), approximately one-third of the AC/AIS cases ever had HPV 16/18/45 and AGC cytology (OR = 1785; 95%CI:872-3656). AGC was not as strongly associated with SCC/CIN3.
CONCLUSION
Detection of HPV 16/18/45 positivity elevates risk of adenocarcinoma, particularly if AGC cytology is also found.
背景
宫颈筛查未能有效控制宫颈腺癌（AC）。人乳头瘤病毒（HPV）检测被推荐用于宫颈筛查，但确定 HPV 阳性个体的最佳管理方案以预防 AC 仍然是一个问题。细胞学和 HPV 分型是两种用于预测 AC 风险的分流选择。我们结合了两种潜在的生物标志物（非典型腺细胞，AGC 细胞学和 HPV 型 16、18 或 45），以评估它们联合检测 AC 的效果。
方法
Kaiser Permanente Northern California（KPNC）在 2003 年至 2020 年期间，使用细胞学和 HPV 检测（阳性/阴性）进行三年一次的联合检测，对常规宫颈筛查进行了联合检测。对从 KPNC（持续性和进展性，PaP 队列）中选择的一个单独队列的残留 HPV 检测标本进行了 HPV 分型。我们比较了与细胞学结果和 HPV 分型相关的先前组合相关的现患和新发组织学 AC/AIS（原位腺癌）的风险。鳞状细胞癌（SCC）/宫颈上皮内瘤变 3 级（CIN3）（SCC/CIN3）的风险也包括在内进行比较。
结果
在 PaP 队列的 HPV 阳性个体中，99%的现患 AC 和 96%的 AIS 与 HPV 型 16、18 或 45 相关（表示 HPV 16/18/45）。尽管罕见（筛查人群的 0.09%），但同时检测到 HPV 16/18/45 和 AGC 细胞学预测潜在组织学 AC/AIS 的相对风险显著升高；诊断 AC/AIS 的绝对风险为 12%，优势比（OR）为 1341（95%CI：495-3630），与其他高危 HPV 类型和正常细胞学的患者相比。累积（允许非并发结果），大约三分之一的 AC/AIS 病例曾经有 HPV 16/18/45 和 AGC 细胞学（OR=1785；95%CI：872-3656）。AGC 与 SCC/CIN3 的相关性并不强。
结论
检测到 HPV 16/18/45 阳性会增加腺癌的风险，特别是如果同时发现 AGC 细胞学。
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