Differences in the concentration and correlation of cervical immune markers among HPV positive and negative perimenopausal women

Introduction: Women ≥45. years of age with persistent HPV infections have distinct peripheral circulating immune profiles. Few studies have comprehensively evaluated the cervical immunologic microenvironment in HPV-positive and HPV-negative perimenopausal women. Methods: We collected cervical secretion specimens from 34 high risk HPV (HR-HPV) positive and 44 HR-HPV negative women enrolled in an ongoing prospective cohort assessing the natural history of HPV across the menopausal transition. We used these specimens to quantify concentrations of 27 different immune markers using multiplexed bead-based immunoassays. Results: HR-HPV positive women had significantly higher median concentrations of IL-5 (0.11ng/mg _{total protein} vs. 0.08ng/mg _{total protein}), IL-9 (2.7ng/mg _{total protein} vs. 2.1ng/mg _{total protein}), IL-13 (2.1ng/mg _{total protein} vs. 0.9ng/mg _{total protein}), IL-17 (2.9ng/mg _{total protein} vs. 1.1ng/mg _{total protein}), EOTAXIN (4.1ng/mg _{total protein} vs. 1.1ng/mg _{total protein}), GM-CSF (4.3ng/mg _{total protein} vs. 3.3ng/mg _{total protein}), and MIP-1α (3.5ng/mg _{total protein} vs. 1.9ng/mg _{total protein}) compared to HR-HPV negative women. A shift in the correlation of T-cell and pro-inflammatory cytokines (IFN-γ, IL-5, IL-9, IL-10, IL-12, IL-13, IL-15, and TNF-α) from IL-2 to EOTAXIN was observed between HR-HPV negative and positive women. Conclusions: Higher local concentrations of anti-inflammatory and allergy associated markers, with a shift in T-cell associated cytokine correlation from IL-2 to EOTAXIN, are associated with HPV infection among older women.