Dema Emily, Shing Jaimie Z, Checchi Marta, Beddows Simon, Liu Danping, Sierra Monica S, Haas Cameron B, Soldan Kate, Field Nigel, Kreimer Aimée R, Sonnenberg Pam
Institute for Global Health, University College London, London, United Kingdom.
Blood Safety, Hepatitis, Sexually Transmitted Infections (STI) and HIV Division, UK Health Security Agency, London, United Kingdom.
Cancer Epidemiol Biomarkers Prev. 2025 Jul 1;34(7):1093-1102. doi: 10.1158/1055-9965.EPI-24-1775.
Evaluating the impact/effectiveness of human papillomavirus (HPV) vaccination generally assumes stability in factors driving transmission, which might not be valid. We aimed to develop, validate, and test a grouping of non-vaccine-preventable HPV (NVP-HPV) types as a molecular indicator associated with sexual behaviors to control for changes in HPV transmission risk.
We used data from the National Surveys of Sexual Attitudes and Lifestyles (Natsal-2, 1999-2001, N = 1,849; Natsal-3, 2010-2012, N = 2,407) to validate the association of NVP-HPV (26/53/66/70/73) with self-reported sexual behaviors. We calculated NVP-HPV-adjusted HPV16/18 vaccine impact/effectiveness estimates in two real-world scenarios: Natsal-2/Natsal-3 (sexually experienced women in Britain, 18-44 years), and England's HPV surveillance (women, 16-24 years; 2008, N = 3,539; 2010-2020, N = 24,707). Samples (urine/vulvovaginal swabs) were tested for 21 HPV genotypes (6/11/16/18/26/31/33/35/39/45/51/52/53/56/58/59/66/68/70/73/82) using an in-house multiplex PCR and Luminex-based genotyping assay.
NVP-HPV infection was strongly associated with sexual behaviors (e.g., younger age at sexual debut and numbers of partners). In Natsal data, adjusting for NVP-HPV did not change vaccine impact estimates [unadjusted prevalence ratio (PR): 0.50 (0.27-0.95) and adjusted PR: 0.45 (0.25-0.82)]. In the second scenario, adjusting for NVP-HPV did not change the PR for HPV 16/18 when comparing 2020 with 2010 [0.07 (0.03-0.15), unadjusted and adjusted PR]. In both scenarios, the prevalence of NVP-HPV did not change over time.
We have demonstrated proof of concept that NVP-HPV is strongly associated with sexual behaviors. Adjusting for NVP-HPV in two datasets found that the original estimates were robust.
NVP-HPV might be used to control for changes in HPV transmission risk over time and between groups when evaluating vaccination impact/effectiveness.
评估人乳头瘤病毒（HPV）疫苗接种的影响/效果通常假定驱动传播的因素具有稳定性，但这可能并不成立。我们旨在开发、验证并测试一组非疫苗可预防的HPV（NVP-HPV）类型，作为与性行为相关的分子指标，以控制HPV传播风险的变化。
我们使用了来自全国性态度和生活方式调查（Natsal-2，1999 - 2001年，N = 1849；Natsal-3，2010 - 2012年，N = 2407）的数据，来验证NVP-HPV（26/53/66/70/73）与自我报告的性行为之间的关联。我们在两种实际场景中计算了经NVP-HPV调整后的HPV16/18疫苗影响/效果估计值：Natsal-2/Natsal-3（英国18 - 44岁有性经历的女性），以及英格兰的HPV监测（16 - 24岁女性；2008年，N = 3539；2010 - 2020年，N = 24707）。使用内部多重PCR和基于Luminex的基因分型检测方法，对样本（尿液/阴道拭子）进行21种HPV基因型（6/11/16/18/26/31/33/35/39/45/51/52/53/56/58/59/66/68/70/73/82）的检测。
NVP-HPV感染与性行为密切相关（例如，首次性行为的年龄较小和性伴侣数量）。在Natsal数据中，调整NVP-HPV后并未改变疫苗影响估计值[未调整的患病率比值（PR）：0.50（0.27 - 0.95），调整后的PR：0.45（0.25 - 0.82）]。在第二种场景中，将2020年与2010年进行比较时，调整NVP-HPV后并未改变HPV 16/18的PR[0.07（0.03 - 0.15），未调整和调整后的PR]。在这两种场景中，NVP-HPV的患病率均未随时间变化。
我们已经证明了NVP-HPV与性行为密切相关这一概念的可行性。在两个数据集中对NVP-HPV进行调整后发现，原始估计值是可靠的。
在评估疫苗接种影响/效果时，NVP-HPV可用于控制HPV传播风险随时间和群体之间的变化。
