Yao Qingyun, Wang Jiangrong, Elfström K Miriam, Strander Björn, Dillner Joakim, Sundström Karin
Center for Cervical Cancer Elimination, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Huddinge, Sweden.
Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
PLoS Med. 2024 Dec 19;21(12):e1004505. doi: 10.1371/journal.pmed.1004505. eCollection 2024 Dec.
Evidence on invasive cervical cancer prevention among older women is limited, especially with the introduction of human papillomavirus (HPV)-based screening and longer interval. We conducted a long-term follow-up of the first phase of a randomized healthcare policy trial in cervical screening, targeting women aged 56 to 61 years old, to investigate the effectiveness of primary HPV-based screening in preventing invasive cervical cancer (ICC) and the safety of extending screening interval.
The randomized healthcare policy trial of primary HPV-based cervical screening targeted women residing in Stockholm-Gotland region during 2012 to 2016, aged 30 to 64 years. The trial aimed to investigate the detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) within 24 months and long-term protection against invasive cervical cancer, comparing primary HPV-based screening to primary cytology-based screening. The initial phase of the trial, which was the focus of this study, targeted women aged 56 to 61 years old in 2012 to 2014 who were randomized to primary cytology arm (n = 7,401) or primary HPV arm (n = 7,318). We used national registries to identify the subsequent cervical tests and all histopathological diagnoses including ICC before December 31, 2022. We calculated cumulative incidence, incidence rate (IR) and IR ratio (IRR) of ICC, by baseline test result. Furthermore, we calculated longitudinal sensitivity and specificity for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) by receipt of primary cytology or primary HPV test for the recommended screening intervals in this age group. We found that the IR of ICC among women in the primary HPV arm was 7.2/100,000 person-years (py) and 3.0 for women who tested HPV negative, compared to 18.4/100,000 py among women in the primary cytology arm and 18.8 for women who tested cytology negative. We further found that the overall point estimate for the risk of ICC over 10 years of follow-up among women in the primary HPV arm was 0.39 compared to women in the primary cytology arm, but this was not statistically significant (IRR: 0.39; 95% confidence interval, CI [0.14, 1.09]; p = 0.0726). However, among women with a negative test result at baseline, women in the primary HPV arm had an 84% lower risk of ICC compared to women in the primary cytology arm (IRR: 0.16; 95% CI [0.04, 0.72]; p = 0.0163). Moreover, primary HPV testing had a higher sensitivity for detecting CIN2+ within a 7-year interval than primary cytology testing within a 5-year interval (89.6% versus 50.9%, p < 0.0001). We were limited by a partial imbalance of invitations during the follow-up between the 2 arms which may have led to an underestimation of the effectiveness of primary HPV-based screening.
In this study, we observed that women over 55 years of age who received a primary negative HPV test result had substantially lower risk of CIN2+, and ICC, compared to women who received a primary negative cytology result. This should apply even if the screening interval were prolonged to 7 years.
NCT01511328.
关于老年女性侵袭性宫颈癌预防的证据有限，尤其是随着基于人乳头瘤病毒（HPV）的筛查方法的引入以及筛查间隔时间的延长。我们对一项宫颈癌筛查随机医疗政策试验的第一阶段进行了长期随访，该试验针对年龄在56至61岁的女性，旨在研究基于HPV的初次筛查预防侵袭性宫颈癌（ICC）的有效性以及延长筛查间隔的安全性。
这项基于HPV的宫颈癌初次筛查随机医疗政策试验针对2012年至2016年期间居住在斯德哥尔摩 - 哥特兰地区、年龄在30至64岁的女性。该试验旨在比较基于HPV的初次筛查和基于细胞学的初次筛查，调查24个月内宫颈上皮内瘤变2级或更高级别（CIN2 +）的检出率以及对侵袭性宫颈癌的长期保护效果。本研究重点关注的试验初始阶段，针对2012年至2014年年龄在56至61岁的女性，她们被随机分配到基于细胞学的初次筛查组（n = 7,401）或基于HPV的初次筛查组（n = 7,318）。我们利用国家登记处来确定后续的宫颈检查以及截至2022年12月31日的所有组织病理学诊断，包括ICC。我们根据基线检查结果计算了ICC的累积发病率、发病率（IR）和发病率比（IRR）。此外，我们计算了在该年龄组推荐的筛查间隔内，通过接受初次细胞学或初次HPV检测来检测宫颈上皮内瘤变2级或更高级别（CIN2 +）的纵向敏感性和特异性。我们发现，基于HPV的初次筛查组女性的ICC发病率为7.2/100,000人年（py），HPV检测阴性的女性为3.0，而基于细胞学的初次筛查组女性的发病率为18.4/100,000 py，细胞学检测阴性的女性为18.8。我们进一步发现，在10年的随访中，基于HPV的初次筛查组女性患ICC风险的总体点估计值为0.39，而基于细胞学的初次筛查组女性为1，但这在统计学上无显著差异（IRR：0.39；95%置信区间，CI [0.14, 1.09]；p = 0.0726）。然而，在基线检测结果为阴性的女性中，基于HPV的初次筛查组女性患ICC的风险比基于细胞学的初次筛查组女性低84%（IRR：0.16；95% CI [0.04, 0.72]；p = 0.0163）。此外，在7年间隔内，初次HPV检测对检测CIN2 +的敏感性高于在5年间隔内的初次细胞学检测（89.6%对50.9%，p < 0.0001）。我们的研究受到随访期间两组之间邀请存在部分不均衡的限制，这可能导致对基于HPV的初次筛查有效性的低估。
在本研究中，我们观察到，与初次细胞学检测结果为阴性的女性相比，初次HPV检测结果为阴性的55岁以上女性患CIN2 +和ICC的风险显著更低。即使筛查间隔延长至7年，这一结论依然适用。
NCT01511328。
