Non HPV-Related Cervical Cancers

Non-HPV-related cervical tumours represent a small share of cervical cancers (CC), accounting for a variable rate of 5–10%. Most of these cases are glandular lesions, better known as adenocarcinomas. It is important to note that some of these cases may be due to diagnostic issues, potentially leading to false-negative cases. However, the latest classification of the World Health Organization categorises CCs into HPV-associated and HPV-independent, each with distinct molecular and clinical characteristics. For instance, HPV-independent tumours often exhibit mutations in specific genes, leading to different molecular profiles. Clinically, they may present with different symptoms and respond differently to treatments. Typically, HPV-independent cervical tumours have a worse prognosis, making conservative treatment in the early stages not advisable. Despite this, there are currently no differentiated treatments based on HPV status. This highlights the need and the importance of a comprehensive understanding of genetic and molecular profiles for developing different risk classes and, in the near future, more targeted and personalised therapies to improve the outcomes of these uncommon cancers.