Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
Regional Laboratory, The Permanente Medical Group, Oakland, CA.
J Natl Cancer Inst. 2018 May 1;110(5):501-508. doi: 10.1093/jnci/djx225.
The main goal of cervical screening programs is to detect and treat precancer before cancer develops. Human papillomavirus (HPV) testing is more sensitive than cytology for detecting precancer. However, reports of rare HPV-negative, cytology-positive cancers are motivating continued use of both tests (cotesting) despite increased testing costs.
We quantified the detection of cervical precancer and cancer by cotesting compared with HPV testing alone at Kaiser Permanente Northern California (KPNC), where 1 208 710 women age 30 years and older have undergone triennial cervical cotesting since 2003. Screening histories preceding cervical cancers (n = 623) and precancers (n = 5369) were examined to assess the relative contribution of the cytology and HPV test components in identifying cases. The performances of HPV testing and cytology were compared using contingency table methods, general estimating equation models, and nonparametric statistics; all statistical tests were two-sided.
HPV testing identified more women subsequently diagnosed with cancer (P < .001) and precancer (P < .001) than cytology. HPV testing was statistically significantly more likely to be positive for cancer at any time point (P < .001), except within 12 months (P = .10). HPV-negative/cytology-positive results preceded only small fractions of cases of precancer (3.5%) and cancer (5.9%); these cancers were more likely to be regional or distant stage with squamous histopathology than other cases. Given the rarity of cancers among screened women, the contribution of cytology to screening translated to earlier detection of at most five cases per million women per year. Two-thirds (67.9%) of women found to have cancer during 10 years of follow-up at KPNC were detected by the first cotest performed.
The added sensitivity of cotesting vs HPV alone for detection of treatable cancer affected extremely few women.
宫颈筛查项目的主要目标是在癌症发展之前发现和治疗癌前病变。与细胞学相比，人乳头瘤病毒（HPV）检测对癌前病变的检测更敏感。然而，HPV 阴性、细胞学阳性的癌症罕见报告促使人们继续使用这两种检测方法（联合检测），尽管检测成本增加了。
我们在 Kaiser Permanente Northern California（KPNC）定量分析了联合检测（HPV 检测加细胞学检测）与单独 HPV 检测相比在检测宫颈癌前病变和癌症方面的效果。自 2003 年以来，该地区年龄在 30 岁及以上的 1208710 名女性每三年进行一次宫颈联合检测。检查了宫颈癌（n=623）和癌前病变（n=5369）的筛查史，以评估细胞学和 HPV 检测在识别病例方面的相对贡献。使用列联表方法、广义估计方程模型和非参数统计方法比较了 HPV 检测和细胞学的性能；所有统计检验均为双侧检验。
HPV 检测比细胞学检测发现更多随后被诊断为癌症（P <.001）和癌前病变（P <.001）的女性。HPV 检测在任何时间点的阳性率都显著更高（P <.001），除了在 12 个月内（P=.10）。HPV 阴性/细胞学阳性结果仅导致一小部分癌前病变（3.5%）和癌症（5.9%）病例；这些癌症更有可能具有鳞状组织病理学的局部或远处阶段，而不是其他病例。鉴于筛查女性中癌症的罕见性，细胞学对筛查的贡献最多可使每年每百万女性中多发现 5 例癌症。在 KPNC 进行 10 年随访期间发现的 2/3（67.9%）癌症患者是通过首次联合检测发现的。
与单独 HPV 检测相比，联合检测在检测可治疗癌症方面的额外敏感性对极少数女性有影响。
