Age-related distribution of uncommon HPV genotypes in cervical intraepithelial neoplasia grade 3

Aim: Cervical cancer prevention guidelines include Human Papillomavirus (HPV) test, cytology, and HPV-16/18 typing for triage to determine the risk of cervical intraepithelial neoplasia (CIN) grade 3 as the best proxy of cervical cancer risk. In doing that, they do not consider how age can modify the type-specific risk of CIN3. The present study aimed to evaluate the age-related distribution of HPV genotypes affecting the risk-assessment in cervical cancer screening programs: non-screening-type-HPV and non-HPV-16/18 in unvaccinated women with CIN3. Methods: Retrospective multi-institutional study, including HPV genotyped women with CIN3 on cone histology treated between 2014 and 2019. The sample was divided into three categories of age: <30, 30–44, ≥45. HPV genotypes were grouped in non-screening-type-HPV (not-including genotypes 16/18/31/33/35/39/45/51/52/56/58/59/66/68) and non-HPV-16/18. Associations and trends between different age-groups and HPV genotypes were measured. Results: 1332 women were analyzed. Non-screening-type-HPV CIN3 were 73 (5.5%). Non-HPV-16/18 were found in 417 participants (31.3%). Women over 45 associated with non-screening-type HPV [odds ratio (OR) = 1.87, 95% confidence interval (CI) 1.07–3.25; p = 0.027]. Non-screening-type-HPV prevalence increased significantly with age (3.9% vs 5.1% vs 9.0%, p = 0.016). Women under 30 showed a lower rate of non-HPV-16/18 (OR = 0.65, 95% CI 0.47–0.89; p = 0.007). There was a positive trend with age of non-HPV-16/18 CIN3 (23.6% vs 32.1% vs 38.0%, p = 0.0004). Conclusion: The proportion of CIN3 lesions unrelated to genotypes detected by primary screening tests increased with age. This implies that age probably modifies the risk of CIN3 and possibly of cancer associated with HPV types. The risk-based recommendation should take into consideration age to define the management of HPV positive women.