HPV-Positive and -Negative Cervical Cancers Are Immunologically Distinct

Area of Science:

• Oncology
• Immunology
• Virology

Background:

• Nearly all cervical cancers (CC) are linked to human papillomavirus (HPV) infection.
• A small subset of CC are HPV-negative, representing a distinct phenotype with poorer prognosis.
• Different HPV types influence CC molecular pathology and patient outcomes.

Purpose of the Study:

• To compare the immune microenvironments of HPV-negative CC, HPV α9 (e.g., HPV16), and HPV α7 (e.g., HPV18) CC.
• To identify differences in immune cell infiltration and molecular markers across CC subtypes.
• To explore the relationship between HPV status, immune landscape, and potential neoantigens in CC.

Main Methods:

• Comparative analysis of immune microenvironments in HPV-negative, HPV α9, and HPV α7 CC.
• Assessment of lymphocyte infiltration (B, T, NK cells) and T-cell markers (effector molecules, activation/exhaustion, TCR diversity).
• Quantification of potential neoantigen expression in different CC subtypes.

Main Results:

• HPV-negative CC exhibited significantly reduced lymphocyte infiltration compared to HPV α9 and α7 CC.
• Lower expression of T-cell markers and reduced T-cell receptor diversity were observed in HPV-negative CC.
• HPV-negative CC showed markedly higher levels of potential neoantigens than HPV-positive CC.

Conclusions:

• Profound differences exist in the immune landscape between HPV-positive and HPV-negative CC.
• Modest immune variations were noted between HPV α9 and α7 CC subtypes.
• These immune landscape differences may explain altered patient outcomes in HPV-negative CC and across different HPV types.