Sørbye Sveinung Wergeland, Falang Bente Marie, Botha Matthys H, Snyman Leon Cornelius, van der Merwe Haynes, Visser Cathy, Richter Karin, Dreyer Greta
Department of Clinical Pathology, University Hospital of North Norway, 9038 Tromsø, Norway.
PreTect AS, 3490 Klokkarstua, Norway.
Cancers (Basel). 2023 Nov 17;15(22):5453. doi: 10.3390/cancers15225453.
Cervical cancer prevention in regions with limited access to screening and HPV vaccination necessitates innovative approaches. This study explored the potential of a test-and-treat strategy using mRNA HPV tests to impact cervical cancer prevention in a high-prevalence HIV population.
A cervical screening study was conducted at three South African hospitals involving 710 under-screened, non-pregnant women (25 to 65 years) without known cervical diseases. Cytology, HPV testing, colposcopy, and biopsies were performed concurrently. Histopathologists determined final histological diagnoses based on biopsy and LLETZ histology. mRNA-HPV-genotyping for 3 (16, 18, 45) to 8 (16, 18, 31, 33, 35, 45, 52, 58) high-risk types was performed on leftover liquid-based cytology material. The preventive potential of the test-and-treat approach was estimated based on published data, reporting the causative HPV types in cervical cancer tissue from South African women. Treatment was provided as needed.
The HPV positivity rate more than doubled from 3-type (15.2%; 95% CI: 12.6-17.8) to 8-type mRNA (31.5%; 95% CI: 28.8-34.9) combinations, significantly higher among HIV-positive women. CIN3+ prevalence among HIV-positive women (26.4%) was double that of HIV-negative women (12.9%) ( < 0.01). The 6-type combination showed the best balance of sensitivity, specificity and treatment group size, and effectiveness to prevent cervical cancer. A 4-type combination (16, 18, 35, 45) could potentially prevent 77.6% (95% CI: 71.2-84.0) of cervical cancer burden by treating 20% and detecting 41.1% of CIN3 cases in the study group. Similarly, a 6-type combination (16, 18, 31, 33, 35, 45), treating 25% and including 62% of CIN3 cases, might prevent 85% of cervical cancer cases (95% CI: 79.6-90.6) among HIV-positive and negative women.
Employing mRNA HPV tests within a test-and-treat approach holds huge promise for targeted cervical cancer prevention in under-screened populations. Testing for mRNA of the 6 highest-risk HPV types in this population and treating them all is projected to effectively prevent progression from CIN3 to invasive cervical cancer while reducing overtreatment in resource-constrained settings.
在筛查和人乳头瘤病毒（HPV）疫苗接种机会有限的地区，宫颈癌预防需要创新方法。本研究探讨了使用mRNA HPV检测的检测即治疗策略对高流行率HIV人群宫颈癌预防的潜力。
在南非的三家医院开展了一项宫颈筛查研究，纳入710名筛查不足、未怀孕、无已知宫颈疾病的女性（25至65岁）。同时进行了细胞学检查、HPV检测、阴道镜检查和活检。组织病理学家根据活检和大环形电切除术组织学确定最终组织学诊断。对剩余的液基细胞学材料进行3种（16、18、45型）至8种（16、18、31、33、35、45、52、58型）高危型别的mRNA-HPV基因分型。根据已发表的数据估计检测即治疗方法的预防潜力，这些数据报告了南非女性宫颈癌组织中的致病HPV类型。根据需要提供治疗。
HPV阳性率从3型组合（15.2%；95%置信区间：12.6 - 17.8）增加到8型mRNA组合（31.5%；95%置信区间：28.8 - 34.9），增加了一倍多，在HIV阳性女性中显著更高。HIV阳性女性中高级别宫颈上皮内瘤变（CIN3+）的患病率（26.4%）是HIV阴性女性（12.9%）的两倍（P < 0.01）。6型组合在敏感性、特异性、治疗组规模和预防宫颈癌有效性方面表现出最佳平衡。4型组合（16、18、35、45型）通过治疗研究组中20%的患者并检测41.1%的CIN3病例，有可能预防77.6%（95%置信区间：71.2 - 84.0）的宫颈癌负担。同样，6型组合（16、18、31、33、35、45型）治疗25%的患者并涵盖62%的CIN3病例，可能预防HIV阳性和阴性女性中85%的宫颈癌病例（95%置信区间：79.6 - 90.6）。
在检测即治疗方法中采用mRNA HPV检测对筛查不足人群的针对性宫颈癌预防具有巨大潜力。对该人群中6种最高危HPV类型的mRNA进行检测并对所有检测阳性者进行治疗，预计可有效预防从CIN3进展为浸润性宫颈癌，同时减少资源受限环境下的过度治疗。
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