Center for Cervical Cancer Elimination, Medical Diagnostics Karolinska, Karolinska University Hospital and Department of CLINTEC, Karolinska Institutet, Stockholm, Sweden.
Center for Cervical Cancer Elimination, Medical Diagnostics Karolinska, Karolinska University Hospital and Department of CLINTEC, Karolinska Institutet, Stockholm, Sweden; Unit for Cancer Screening, Regional Cancer Center Stockholm-Gotland, Stockholm, Sweden.
Lancet Public Health. 2024 Nov;9(11):e886-e895. doi: 10.1016/S2468-2667(24)00218-4.
Human papillomavirus (HPV)-based cervical screening is a globally recommended public health policy. Randomised clinical trials find superior performance of primary HPV-based screening compared with cytology for preventing cervical cancer. However, additional evidence from real-world public health policies is needed. In preplanned secondary analysis of a randomised health-care policy trial in Sweden we aimed to evaluate which policy provided better protection against invasive cervical cancer, after two full rounds of screening.
The organised cervical screening programme in the capital region of Sweden invited all women aged 30-64 years and eligible for screening to a randomised health-care policy trial of HPV-based versus cytology-based screening. During 2014-16, 395 725 eligible women were randomly assigned (non-concealed) to either policy and the invasive cervical cancer incidences over 8 years of follow-up were compared. Intention-to-screen analyses included all invited women and per-protocol analyses the women that attended baseline screening according to protocol. This trial is registered with ClinicalTrials.gov, NCT01511328.
Women invited to HPV-based cervical screening had a 17% lower invasive cervical cancer risk compared with women invited to cytology (hazard ratio [HR] 0·83, 95% CI 0·70-0·98). Women participating in HPV-based screening had a 28% lower invasive cervical cancer risk compared with women participating with cytology (HR 0·72, 95% CI 0·54-0·95). Adverse events were a higher number of referrals to colposcopy with biopsy in the HPV policy (15 832 [7·5%] of 212 199 in intention to screen analyses and 9968 [9·0%] of 110 176 per protocol at baseline) than in the cytology policy (12 650 [6·9%] of 183 120 in intention to screen analyses, and 7179 [7·9%] of 90 821 per protocol at baseline). Women who were HPV-negative at baseline had invasive cervical cancer risks of 1·3 (95% CI 0·6-2·4) per 100 000 person-years, whereas the risk for women with normal cytology was 9·1 (6·7-11·8) per 100 000 person-years. HPV-positive women with negative cytology triage had invasive cervical cancer risks of 79·2 per 100 000 person-years and HPV 16 or HPV 18-positive women with negative cytology triage had risks of 318·2 per 100 000 person-years.
This randomised policy trial found HPV-based screening to be superior for preventing invasive cervical cancer in the real-world setting. A single baseline HPV-negative test was associated with a very low invasive cervical cancer risk after 8 years. However, HPV positivity with negative cytology triage was associated with high invasive cervical cancer risks.
Region Stockholm, Swedish Cancer Society, and European Union Horizon 2020.
人乳头瘤病毒（HPV）为基础的宫颈癌筛查是一项全球推荐的公共卫生政策。随机临床试验发现，与细胞学相比，初级 HPV 为基础的筛查在预防宫颈癌方面具有更好的效果。然而，需要来自真实世界公共卫生政策的额外证据。在瑞典一项随机卫生保健政策试验的预先计划的二次分析中，我们旨在评估在两轮完整的筛查后，哪种政策能更好地预防浸润性宫颈癌。
瑞典首都地区组织的宫颈癌筛查计划邀请所有 30-64 岁符合筛查条件的妇女参加 HPV 为基础与细胞学为基础的筛查的随机卫生保健政策试验。在 2014-16 年期间，395725 名符合条件的妇女被随机分配（非隐匿）到两种政策中，并对 8 年随访期间的浸润性宫颈癌发病率进行比较。意向性筛查分析包括所有受邀妇女，而方案性筛查分析则包括根据方案参加基线筛查的妇女。这项试验在 ClinicalTrials.gov 上注册，编号为 NCT01511328。
与细胞学组相比，接受 HPV 为基础的宫颈癌筛查的妇女浸润性宫颈癌风险降低了 17%（危险比[HR]0.83，95%置信区间 0.70-0.98）。与细胞学组相比，参加 HPV 筛查的妇女浸润性宫颈癌风险降低了 28%（HR 0.72，95%置信区间 0.54-0.95）。不良事件是 HPV 组进行更多的阴道镜检查和活检，（意向性筛查分析中 212199 人中 15832 人[7.5%]，基线时 110176 人中有 9968 人[9.0%]）比细胞学组多（意向性筛查分析中 183120 人中有 12650 人[6.9%]，基线时 90821 人中有 7179 人[7.9%]）。基线时 HPV 阴性的妇女浸润性宫颈癌风险为每 10 万人年 1.3（95%置信区间 0.6-2.4），而细胞学正常的妇女风险为每 10 万人年 9.1（6.7-11.8）。HPV 阳性、细胞学阴性的妇女有 79.2 人/10 万人年发生浸润性宫颈癌的风险，HPV16 或 HPV18 阳性、细胞学阴性的妇女有 318.2 人/10 万人年发生浸润性宫颈癌的风险。
这项随机政策试验发现，在真实环境中，HPV 为基础的筛查在预防浸润性宫颈癌方面更有效。在 8 年后，单次基线 HPV 阴性检测与浸润性宫颈癌的低风险相关。然而，HPV 阳性、细胞学阴性的阴道镜检查和活检与高浸润性宫颈癌风险相关。
斯德哥尔摩地区、瑞典癌症协会和欧盟地平线 2020。
