A comprehensive natural history model of HPV infection and cervical cancer to estimate the clinical impact of a prophylactic HPV-16/18 vaccine
A comprehensive natural history model of HPV infection and cervical cancer to estimate the clinical impact of a prophylactic HPV-16/18 vaccine
复制标题
DOI：
10.1002/ijc.11334
复制
发表时间：
2003-10-10
影响因子：
6.4
通讯作者：
Franco, E
中科院分区：
文献类型：
--
作者：
Goldie, SJ;Grima, D;Franco, E
我们研究的目的是预测针对持续性人乳头瘤病毒 (HPV)-16/18 感染的预防性疫苗对特定年龄的浸润性宫颈癌发病率的影响。我们开发了一个基于计算机的宫颈癌发生自然史数学模型，将癌前病变和浸润癌中潜在的特定类型 HPV 分布纳入其中。根据全面的文献综述确定每个参数的合理范围后，模型被校准为基于人口的最佳可用数据。我们预测了使用可降低 HPV 16/18 持续感染可能性的疫苗可减少特定年龄的宫颈癌，并探讨了有关疫苗功效和覆盖范围、免疫力减弱以及与已接种疫苗的女性中非 16/18 HPV 类型相关的竞争风险的其他假设的影响。该模型预测，第 6 个十年中特定年龄癌症发病率为每 100,000 人中 90 人，终生癌症风险为 3.7%，并且低度和高度宫颈癌前病变和宫颈癌中特定型 HPV 的表现可重复。疫苗可以预防 98% 的持续性 HPV 16/18，并且与 16/18 相关的癌症大约有相当的减少，宫颈癌总数也减少了 51%；由于与其他致癌非 16/18 类型相关的竞争风险，对总癌症的影响减弱。预防 75% 持续性 HPV 16/18 的疫苗可将 HPV-16/18 癌症病例减少 70% 至 83%。尽管疫苗接种对 HPV 和低度鳞状上皮内病变 (LSIL) 总体患病率的影响很小，但在高级鳞状上皮内病变 (HSIL) 中观察到了类似的效果。总之，预防持续性 HPV-16/18 感染的预防性疫苗有望显着减少 HPV-16/18 相关的 LSIL、HSIL 和宫颈癌。然而，对 HPV 或 LSIL 总体患病率的影响可能很小。根据模型中不同参数的相对重要性，确定了未来研究的几个重点。这些包括更好地了解疫苗反应的异质性、特定类型疫苗接种对其他 HPV 类型的影响以及疫苗接种效果随时间持续的程度。 (C) 2003 Wiley-Liss, Inc.
The object of our study is to project the impact of a prophylactic vaccine against persistent human papillomavirus (HPV)-16/18 infection on age-specific incidence of invasive cervical cancer. We developed a computer-based mathematical model of the natural history of cervical carcinogenesis to incorporate the underlying type-specific HPV distribution within precancerous lesions and invasive cancer. After defining plausible ranges for each parameter based on a comprehensive literature review, the model was calibrated to the best available population-based data. We projected the age-specific reduction in cervical cancer that would occur with a vaccine that reduced the probability of acquiring persistent infection with HPV 16/18, and explored the impact of alternative assumptions about vaccine efficacy and coverage, waning immunity and competing risks associated with non-16/18 HPV types in vaccinated women. The model predicted a peak age-specific cancer incidence of 90 per 100,000 in the 6th decade, a lifetime cancer risk of 3.7% and a reproducible representation of type-specific HPV within low and high-grade cervical precancerous lesions and cervical cancer. A vaccine that prevented 98% of persistent HPV 16/18 was associated with an approximate equivalent reduction in 16/18-associated cancer and a 51% reduction in total cervical cancer; the effect on total cancer was attenuated due to the competing risks associated with other oncogenic non-16/18 types. A vaccine that prevented 75% of persistent HPV 16/18 was associated with a 70% to 83% reduction in HPV-16/18 cancer cases. Similar effects were observed with high-grade squamous intraepithelial lesions (HSIL) although the impact of vaccination on the overall prevalence of HPV and low-grade squamous intraepithelial lesions (LSIL) was minimal. In conclusion, a prophylactic vaccine that prevents persistent HPV-16/18 infection can be expected to significantly reduce HPV-16/18-associated LSIL, HSIL and cervical cancer. The impact on overall prevalence of HPV or LSIL, however, may be minimal. Based on the relative importance of different parameters in the model, several priorities for future research were identified. These include a better understanding of the heterogeneity of vaccine response, the effect of type-specific vaccination on other HPV types and the degree to which vaccination effect persists over time. (C) 2003 Wiley-Liss, Inc.