英国伦敦国王学院Matejka Rebolj团队研究了延长宫颈筛查人乳头瘤病毒检测周期的影响。2022年5月31日出版的《英国医学杂志》发表了这项成果。

为了根据年龄组和检测方法，提供关于初级宫颈筛查中人乳头瘤病毒（HPV）检测阴性后发生宫颈上皮内瘤变3级及以上（CIN3+）和宫颈癌风险的最新证据，研究组对英国HPV筛查试点第一轮和第二轮的真实世界数据（2013-2016年，随访至2019年底）进行了一项观察性研究。

参与者共涉及1341584名女性。通过HPV检测或液基细胞学检测（细胞学或涂片检测）进行宫颈筛查。经细胞学筛查的女性在试验中发生高级别细胞学异常、或临界或低级别异常并伴有HPV阳性后，应进行阴道镜检查。

经HPV检测筛查呈阳性的女性，如果其细胞学分诊检查至少显示临界异常，则在基线检查时被转诊；如果有持续异常，则在12个月和24个月后再次复检（早期回访）后被转诊。主要观察指标为在HPV检测阴性后检测到CIN3+和宫颈癌的风险。

对于50岁以下的女性，在第一轮HPV筛查阴性后，本研究的第二轮CIN3+检出率为1.21/1000筛查女性，明显低于细胞学检测（4.52/1000筛查女性），校正优势比为0.26；间隔期宫颈癌检出率为1.31/100000女性-年，亦明显低于细胞学检测（2.90/100000女性-年），校正危险比为0.44。

在HPV检测阴性五年后的第二轮试验中，在50岁以上的女性中检测到CIN3+事件的风险甚至低于50岁以下的女性，分别为0.57/1000女性与1.21/1000女性，校正优势比为0.46。

与最初检测HPV阴性的女性相比，早期HPV检测阴性、之后HPV检测阳性且无细胞学异常的女性在第二次常规回访中的CIN3+检出率更高，分别为5.39/1000筛查女性与1.21/1000筛查女性，校正优势比为3.27。

经临床验证的APTIMA mRNA HPV阴性后的检测与经临床验证的cobas和实时DNA检测后的检测结果相似，第二轮筛查的CIN3+发生率分别为1.32/1000筛查女性与1.14/1000筛查女性，校正优势比为1.05。

综上，研究结果支持延长筛查间隔，无论使用何种检测方法：25-49岁的女性在HPV检测阴性后间隔五年，50岁及以上的女性甚至更长。早期回访时HPV检测阴性的HPV阳性女性的筛查间隔应保持在三年。

附：英文原文

Title: Extension of cervical screening intervals with primary human papillomavirus testing: observational study of English screening pilot data

Author: Matejka Rebolj, Kate Cuschieri, Christopher S Mathews, Francesca Pesola, Karin Denton, Henry Kitchener

Issue&Volume: 2022/05/31

Abstract:

Objectives To provide updated evidence about the risk of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and cervical cancer after a negative human papillomavirus (HPV) test in primary cervical screening, by age group and test assay.

Design Observational study.

Setting Real world data from the English HPV screening pilot’s first and second rounds (2013-16, follow-up to end of 2019).

Participants 1341584 women.

Interventions Cervical screening with HPV testing or liquid based cytological testing (cytology or smear tests). Women screened with cytology were referred to colposcopy after high grade cytological abnormalities or after borderline or low grade abnormalities combined with a positive HPV triage test. Women screened with HPV testing who were positive were referred at baseline if their cytology triage test showed at least borderline abnormalities or after a retest (early recall) at 12 and 24 months if they had persistent abnormalities.

Main outcome measures Detection of CIN3+ and cervical cancer after a negative HPV test.

Results For women younger than 50 years, second round detection of CIN3+ in this study was significantly lower after a negative HPV screen in the first round than after cytology testing (1.21/1000 v 4.52/1000 women screened, adjusted odds ratio 0.26, 95% confidence interval 0.23 to 0.30), as was the risk of interval cervical cancer (1.31/100000 v 2.90/100000 woman years, adjusted hazard ratio 0.44, 0.23 to 0.84). Risk of an incident CIN3+ detected at the second screening round in the pilot five years after a negative HPV test was even lower in women older than 50 years, than in three years in women younger than 50 years (0.57/1000 v 1.21/1000 women screened, adjusted odds ratio 0.46, 0.27 to 0.79). Women with negative HPV tests at early recall after a positive HPV screening test without cytological abnormalities had a higher detection rate of CIN3+ at the second routine recall than women who initially tested HPV negative (5.39/1000 v 1.21/1000 women screened, adjusted odds ratio 3.27, 95% confidence interval 2.21 to 4.84). Detection after a negative result on a clinically validated APTIMA mRNA HPV test was similar to that after clinically validated cobas and RealTime DNA tests (for CIN3+ at the second round 1.32/1000 v 1.14/1000 women screened, adjusted odds ratio 1.05, 0.73 to 1.50).

Conclusions These data support an extension of the screening intervals, regardless of the test assay used: to five years after a negative HPV test in women aged 25-49 years, and even longer for women aged 50 years and older. The screening interval for HPV positive women who have negative HPV tests at early recall should be kept at three years.

DOI: 10.1136/bmj-2021-068776

Source: https://www.bmj.com/content/377/bmj-2021-068776