背景:在筛查和HPV疫苗接种机会有限的地区预防宫颈癌需要创新的方法。这项研究探索了使用mRNAHPV测试来影响高患病率HIV人群中宫颈癌预防的测试和治疗策略的潜力。
方法:在南非三家医院进行了一项宫颈筛查研究,涉及710家筛查不足的医院,非孕妇(25至65岁),没有已知的宫颈疾病。细胞学,HPV检测,阴道镜检查,同时进行活检。组织病理学家根据活检和LLETZ组织学确定最终的组织学诊断。对剩余的液基细胞学材料进行3种(16、18、45)至8种(16、18、31、33、35、45、52、58)高风险类型的mRNA-HPV基因分型。测试和治疗方法的预防潜力是根据公布的数据估计的,报告南非妇女宫颈癌组织中的致病HPV类型。根据需要提供治疗。
结果:HPV阳性率从3型(15.2%;95%CI:12.6-17.8)到8型mRNA(31.5%;95%CI:28.8-34.9)组合增加了一倍以上,在艾滋病毒阳性妇女中明显更高。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型组合显示出最佳的灵敏度平衡,特异性和治疗组大小,和预防宫颈癌的有效性。4型组合(16,18,35,45)可能通过治疗20%和检测41.1%的CIN3病例来预防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%,包括62%的CIN3病例,在HIV阳性和阴性妇女中,可能预防85%的宫颈癌病例(95%CI:79.6-90.6)。
结论:在检测和治疗方法中使用mRNAHPV检测对于在筛查不足的人群中预防宫颈癌具有巨大的前景。在该人群中检测6种风险最高的HPV类型的mRNA并对其进行治疗,预计将有效防止CIN3进展为浸润性宫颈癌,同时在资源有限的环境中减少过度治疗。
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.
CONCLUSIONS: 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.