Given that high-risk human papillomavirus (HPV) is the necessary cause of virtually all cervical cancer, the clinical meaning of HPV-negative cervical precancer is unknown. We, therefore, conducted a literature search in Ovid MEDLINE, PubMed Central, and Google Scholar to identify English-language studies in which (i) HPV-negative and -positive, histologically confirmed cervical intraepithelial neoplasia grade 2 or more severe diagnoses (CIN2+) were detected and (ii) summarized statistics or deidentified individual data were available to summarize proportions of biomarkers indicating risk of cancer. Nineteen studies including 3,089 (91.0%) HPV-positive and 307 (9.0%) HPV-negative CIN2+ were analyzed. HPV-positive CIN2+ (vs. HPV-negative CIN2+) was more likely to test positive for biomarkers linked to cancer risk: a study diagnosis of CIN3+ (vs. CIN2; 18 studies; 0.56 vs. 0.24; P < 0.001) preceding high-grade squamous intraepithelial lesion cytology (15 studies; 0.54 vs. 0.10; P < 0.001); and high-grade colposcopic impression (13 studies; 0.30 vs. 0.18; P = 0.03). HPV-negative CIN2+ was more likely to test positive for low-risk HPV genotypes than HPV-positive CIN2+ (P < 0.001). HPV-negative CIN2+ appears to have lower cancer risk than HPV-positive CIN2+. Clinical studies of human high-risk HPV testing for screening to prevent cervical cancer may refer samples of HPV test–negative women for disease ascertainment to correct verification bias in the estimates of clinical performance. However, verification bias adjustment of the clinical performance of HPV testing may overcorrect/underestimate its clinical performance to detect truly precancerous abnormalities.

中文翻译：

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比较人乳头瘤病毒阳性和阴性宫颈癌前期临床特征的汇总分析


鉴于高危人乳头瘤病毒 (HPV) 是几乎所有宫颈癌的必要病因，HPV 阴性宫颈癌前病变的临床意义尚不清楚。因此，我们在 Ovid MEDLINE、PubMed Central 和 Google Scholar 中进行了文献检索，以识别英语研究，其中 (i) HPV 阴性和阳性、组织学证实的宫颈上皮内瘤变 2 级或更严重的诊断 (CIN2+)检测到并且（ii）总结统计数据或未识别的个人数据可用于总结表明癌症风险的生物标志物的比例。分析了 19 项研究，包括 3,089 项 (91.0%) HPV 阳性和 307 项 (9.0%) HPV 阴性 CIN2+。 HPV 阳性 CIN2+（相对于 HPV 阴性 CIN2+）更有可能检测出与癌症风险相关的生物标志物呈阳性：一项研究诊断 CIN3+（相对于 CIN2；18 项研究；0.56 与 0.24；P < 0.001）先于高风险人群鳞状上皮内病变细胞学分级（15 项研究；0.54 vs. 0.10；P < 0.001）；和高级阴道镜印模（13 项研究；0.30 vs. 0.18；P = 0.03）。 HPV 阴性 CIN2+ 比 HPV 阳性 CIN2+ 更有可能检测出低危 HPV 基因型呈阳性 (P < 0.001)。 HPV 阴性 CIN2+ 的癌症风险似乎低于 HPV 阳性 CIN2+。用于筛查预防宫颈癌的人类高危 HPV 检测的临床研究可能会参考 HPV 检测阴性女性样本进行疾病确定，以纠正临床表现估计中的验证偏差。然而，HPV 检测临床表现的验证偏倚调整可能会过度校正/低估其检测真正癌前异常的临床表现。