Background: 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. Methods: 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. Results: 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%) (p< 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. Conclusion: 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.
背景：在筛查和人乳头瘤病毒（HPV）疫苗接种可及性有限的地区，宫颈癌预防需要创新策略。本研究探讨了在高HIV感染率人群中，采用基于mRNA HPV检测的"即筛即治"策略对宫颈癌预防的潜在影响。方法：在南非三家医院开展宫颈筛查研究，纳入710名筛查不足、无已知宫颈疾病且未怀孕的妇女（25-65岁）。同步进行细胞学检查、HPV检测、阴道镜检查和活检。组织病理学家根据活检和大环电切术（LLETZ）标本确定最终组织学诊断。利用剩余液基细胞学标本进行3种（16、18、45型）至8种（16、18、31、33、35、45、52、58型）高危型mRNA-HPV基因分型检测。基于已发表的南非女性宫颈癌组织中致病HPV型别数据，评估"即筛即治"策略的预防潜力。根据临床需要提供治疗。结果：HPV阳性率从3型组合（15.2%；95% CI：12.6-17.8）增至8型mRNA组合（31.5%；95% CI：28.8-34.9），增幅超一倍，HIV阳性妇女中阳性率显著更高。HIV阳性妇女的CIN3+患病率（26.4%）是HIV阴性妇女（12.9%）的两倍（p<0.01）。6型组合在敏感性、特异性、治疗群体规模及预防宫颈癌效果方面达到最佳平衡。4型组合（16、18、35、45）通过治疗20%的研究对象并检出41.1%的CIN3病例，可预防77.6%（95% CI：71.2-84.0）的宫颈癌负担。同样，6型组合（16、18、31、33、35、45）治疗25%的研究对象并覆盖62%的CIN3病例，可能在HIV阳性和阴性妇女中预防85%的宫颈癌病例（95% CI：79.6-90.6）。结论：在"即筛即治"策略中应用mRNA HPV检测，为筛查不足人群的精准宫颈癌预防带来巨大前景。在该人群中检测6种最高危HPV型别的mRNA并实施治疗，预计能有效阻止CIN3向浸润性宫颈癌进展，同时在资源有限环境中减少过度治疗。
肿瘤(癌症)患者之家