Dear Dr G,I read with interest how you highlighted the possibility of men having of cancer following human papillomavirus (HPV) infection.You did note HPV-related cancers are far more common in women and fully agree that raising public awareness is important.However, I am concerned by the suggestion that men, as what some refer to as the “stronger” sex, may need less protection than women.I read a study that found there was a higher HPV prevalence in men and lower rates of lasting immune response after natural infection.If this is the case, is it true HPV infect men and women equally?Do men carry the virus more than women as they age?Lastly, is there evidence that men develop stronger natural immunity to HPV than women?Yours truly, Weaker William HPV is one of the most common sexually transmitted infections worldwide, affecting both men and women across all age groups. Despite this shared exposure, important differences exist in terms of immunological response. While HPV has traditionally been framed as a major women’s health issue due to its association with cervical cancer, growing evidence shows that men have weaker natural immunity to HPV. This reduced immune response contributes to persistent infection, repeated exposure and a significant burden of HPV-related disease throughout life. The burden of HPV infection in men is substantial and remains relatively constant across the lifespan – unlike women, whose HPV prevalence typically peaks in early adulthood and declines with age. Men continue to acquire new infections throughout life, indicating a lack of effective protective immunity. As a result, men serve as both reservoirs and transmitters of the virus. Clinically, HPV infection in men can manifest as genital warts caused by low-risk HPV types, as well as more serious conditions such as penile, anal and oropharyngeal cancers linked to high-risk types. Notably, the incidence of HPV-related oropharyngeal cancers has been increasing in men and often presents later in life, reflecting the long-term consequences of persistent infection. A key explanation for this sustained disease burden lies in the differences in immune response between men and women following natural HPV infection. Women are more likely to undergo seroconversion, meaning they develop detectable antibodies against HPV, particularly high-risk types such as HPV16 and HPV18. These antibodies can provide partial protection against reinfection, suggesting the development of some level of immune memory. In contrast, men exhibit lower rates of seroconversion and produce lower levels of antibodies. Even when antibodies are present, they do not appear to offer significant protection against subsequent infections, indicating a weaker and less durable immune response. The reasons for this disparity are both anatomical and biological. The female genital tract is primarily composed of mucosal epithelium, which allows for greater exposure of viral antigens to the immune system and promotes stronger immune activation. In contrast, much of the male genital epithelium is keratinised, limiting antigen presentation and reducing the effectiveness of immune recognition. Additionally, broader immunological differences between sexes play a role, as females generally mount stronger innate and adaptive immune responses. Hormonal influences such as estrogen enhance immune activity, while testosterone in males has been associated with relatively immunosuppressive effects, further contributing to weaker immunity in men. As a consequence of these factors, men often clear individual HPV infections without developing lasting immune protection. This leads to a cycle of infection, clearance and reinfection rather than the development of durable immunity. Over time, repeated exposure increases the likelihood of persistent infection with high-risk HPV types, which is a critical factor in carcinogenesis. The inability to effectively eliminate the virus or prevent reinfection places men at a higher cumulative risk of developing HPV-related cancers. The implications for cancer are significant, particularly given the absence of routine screening programs for men. While women benefit from cervical screening that allows for early detection and intervention, men typically lack comparable preventive measures. This often results in HPV-related cancers being diagnosed at later stages, when treatment is more challenging and outcomes are poorer. The rising incidence of oropharyngeal cancers in men highlights the growing importance of addressing HPV as a men’s health issue. In conclusion, men can be considered the weaker gender in terms of natural immunity to HPV infection due to their lower rates of seroconversion, weaker antibody responses and lack of effective immune memory. These immunological disadvantages, combined with anatomical and hormonal factors, lead to persistent susceptibility, repeated infections and an increased lifetime burden of disease. Recognising this disparity is essential for informing public health strategies, particularly the promotion of vaccination and awareness, to reduce the impact of HPV-related diseases in men and the broader population.
