Background Human papillomavirus (HPV) is strongly associated with ano-genital and cervical cancer. Persistence of oncogenic HPV genotypes is required for development and progression of HPV-associated malignancies. Although, >70% of women clear incident HPV infections, data on natural history and HPV immunology among men is limited. Methods To evaluate cell-mediated immune response against natural HPV infection among men, we assessed cytokine (IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-13) responses in peripheral-blood-mononuclear cells (PBMCs) collected from 135 men enrolled in a prospective HPV cohort study. PBMCs were stimulated by HPV L1 gene viral-like-particles (VLP) and cytokine responses measured using a multiplex Luminex assay. Results Of 135 men included in this analysis, 41 men had persistent HPV infection, 44 men cleared HPV infection and 50 were HPV uninfected. Their mean (SD) ages were 28.9 (6.79), 27.6 (6.49) and 26.4 (4.81) years respectively. Immune response was induced in 22% (95% CI: 12.8–35.2) of HPV uninfected men, 64% (95% CI: 48.9–76.2) of men with HPV clearance and 51% (95% CI: 36.5–65.8) of men with HPV persistence. Men with HPV clearance and HPV persistence were significantly (p Conclusion In this study, Th1 cell-mediated cytokine immune response was associated with HPV clearance in men. Disclosure No significant relationships.