Reduced MHC Class I and II Expression in HPV-Negative vs. HPV-Positive Cervical Cancers

Cervical cancer (CC) is the second most common cancer in women worldwide and the fourth leading cause of cancer-associated death in women. Although human papillomavirus (HPV) infection is associated with nearly all CC, it has recently become clear that HPV-negative (HPV-) CC represents a distinct disease phenotype with increased mortality. HPV-positive (HPV+) and HPV- CC demonstrate different molecular pathology, prognosis, and response to treatment. Furthermore, CC caused by HPV alpha 9 types (HPV16-like) often have better outcomes than those caused by HPV alpha 7 types (HPV18-like). This study systematically and comprehensively compared the expression of genes involved in major histocompatibility complex (MHC) class I and II presentation within CC caused by HPV alpha 9 types, HPV alpha 7 types, and HPV- CC. We observed increased expression of MHC class I and II classical and non-classical genes in HPV+ CC and overall higher expression of genes involved in their antigen loading and presentation apparatus as well as transcriptional regulation. Increased expression of MHC I-related genes differs from previous studies using cell culture models. These findings identify crucial differences between antigen presentation within the tumor immune microenvironments of HPV+ and HPV- CC, as well as modest differences between HPV alpha 9 and alpha 7 CC. These differences may contribute to the altered patient outcomes and responses to immunotherapy observed between these distinct cancers.

Automated summary

This study compared the gene expression differences between HPV-positive and HPV-negative cervical cancer and identified crucial differences in antigen presentation within the tumor immune microenvironments. These differences may contribute to the altered patient outcomes and responses to immunotherapy observed between these distinct cancers.