Abstract
INTRODUCTION: Previous studies have shown that individuals with human papillomavirus (HPV)-related cervical lesions have different prognoses according to the HPV genotype. However, these studies failed to account for possible diagnostic misclassification. In this retrospective cohort study, we aimed to clarify the natural course of cervical lesions according to HPV genotype to account for any diagnostic misclassification. MATERIALS AND METHODS: Our cohort included 729 patients classified as having cervical intraepithelial neoplasia (CIN). HPV was genotyped in all patients, who were followed up or treated for cervical lesions at the University of Tokyo Hospital from October 1, 2008 to March 31, 2015. Hidden Markov models were applied to estimate the diagnostic misclassification probabilities of the current diagnostic practice (histology and cytology) and the transitions between true states. We then simulated two-year transition probabilities between true cervical states according to HPV genotype. RESULTS: Compared with lesions in patients with other HPV genotypes, lesions in HPV 16-positive patients were estimated to be more likely to increase in severity (i.e., CIN3/cancer); over 2 years, 17.7% (95% confidence interval [CI], 9.3%-29.3%) and 27.8% (95% CI, 16.6%-43.5%) of those with HPV 16 progressed to CIN3/cancer from the true states of CIN1 and CIN2, respectively, whereas 55%-70% of CIN1/2 patients infected with HPV 52/58 remained in the CIN1/2 category. Misclassification was estimated to occur at a rate of 3%-38% in the current diagnostic practice. CONCLUSION: This study contributes robust evidence to current literature on cervical lesion prognosis according to HPV genotype and quantifies the diagnostic misclassification of true cervical lesions.