Age of acquisition of disease-causal human papillomavirus infection to high-grade cervical intraepithelial neoplasia (CIN2+) in England.

backgroundThe human papillomavirus (HPV) is the primary causative risk factor for developing cervical intraepithelial neoplasia (CIN), which can progress to cervical cancer in women. The age at which women in England acquire a causal HPV infection that progresses into CIN and subsequently cervical cancer is not well understood. HPV immunisation was introduced in England in 2008 and catch-up vaccination is available up to the age of 25.

methodsA published discrete event model was modified to estimate the median age of acquisition of causal HPV infection for CIN2+ (CIN2, CIN2/3, CIN3, and adenocarcinoma in situ) among women diagnosed with CIN2 + in England. The model simulates 1,000 women progressing through causal HPV infection, CIN2 + onset, and CIN2 + diagnosis to determine the optimal time delay between causal infection and CIN2 + diagnosis by comparing the predicted age distribution of CIN2 + incidence to real-world diagnosis data. Scenario analyses were conducted to test the impact of uncertainty on the model results by implementing alternate parameterisations for the time from causal HPV infection to CIN2 + onset. Two sensitivity analyses were conducted; the first assumed the time from causal infection to onset of CIN2 + was age-dependent, and the second used an alternate parametric exponential distribution in the model.

resultsThe model predicted that the median ages of causal infection and disease diagnosis (95% confidence interval [CI]) were 26.43 (26.36, 26.50) and 32.42 (32.37, 32.47) years, respectively, based on an offset (defined as the time between causal HPV infection and CIN2 + diagnosis) of 6.17 (6.08, 6.26) years. A substantial proportion of causal HPV infections occurred after the age of 25 (56.24%, 95% CI 55.93, 56.55). The model results were robust to variations in inputs and parameterisation tested in scenario and sensitivity analyses.

conclusionsThere is a substantial burden of disease-causal HPV infection and high-grade cervical disease among women in England over the age of 25 years. Vaccinating women before acquiring disease-causal HPV infection can prevent progression to CIN2+, and subsequent cervical cancer. This supports the need for continued vaccination catch-up opportunities, in addition to potential benefits of HPV vaccination strategies beyond the eligible age within the national immunisation programme. CLINICAL TRIAL NUMBER: Not applicable.