Role of human papillomavirus status in the classification, diagnosis, and prognosis of malignant cervical epithelial tumors and precursor lesions.

Cervical cancer ranks as the fourth most common malignant tumor in the female genital tract. Despite numerous efforts to reduce both the incidence and mortality in recent decades, it is still considered a major health issue worldwide. Previous classifications and diagnostic criteria relied on morphologic features only, lacking clinical and/or pathogenetic correlations. The present review focuses on some new developments regarding the significant role of human papillomavirus (HPV) status for the diagnosis, classification, and prognosis of the most frequent malignant cervical epithelial tumors (squamous cell carcinoma and endocervical adenocarcinoma) and their precursor lesions. The current World Health Organization (WHO) 2020 classification and morphologic criteria proposed by the International Endocervical Classification and Criteria (IECC) in 2018 are detailed. Ancillary studies to help the differential diagnosis are presented, including the critical role of p16, HPV test, and, more recently, p53. Although the management of HPV-associated and HPV-independent cervical cancer is similar at present according to current international guidelines, recent studies have highlighted the significance of HPV status for determining patient survival and response to treatment. As a consequence, personalized management approaches based on these factors could enhance treatment outcomes. Future national screening programs should integrate the information on recently described HPV-independent squamous and glandular precursor lesions.