Which is the best management for women with normal cervical cytologic findings despite positivity for non-16/18 high risk human papillomaviruses?

Women who test positive for the human papillomavirus (HPV) but have normal cytology constitute the predominant subgroup of patients in the screening population in the post-vaccination era. The distribution of HPV genotypes changed dramatically, which was attributable to an increase in HPV vaccination coverage. These changes have created uncertainty about how to properly manage women with normal cytology, non-HPV16/18 infections, or persistent infections. Current recommendations include retesting and continued surveillance in the absence of HPV16/18 infection. However, these are not always applicable. The ability to implement genotyping or incorporate HPV16/18 with some additional high-risk HPV (HR-HPV) types for triage and management with the aim of identifying type-specific risks in this population could be acceptable. When the next set of guidelines is updated, generating potential triage strategies for detecting high-grade cervical lesions, such as the p16/Ki67 cytology assay and other alternatives that incorporate genotyping with newer tests, should be considered. Current clinical management is shifting to risk-based strategies; however, no specific risk threshold has been established in this population. Importantly, innovative triage testing should be evaluated in combination with primary screening and management. Furthermore, there is an untapped opportunity to coordinate HPV genotyping in combination with colposcopic characteristics to modify risk in this group. Hence, providing a more personalized schedule through the efficient application of risk stratification and improving the detection of pre-cancer and cancer is an option worth exploring.