New data on sperm quality and oxidative stress

In a recent study published in the Frontiers of Cellular and Infection Microbiology, a group of researchers investigated the association of high-risk (HR) and low-risk (LR) human papillomavirus (HPV) (a common sexually transmitted virus that can cause genital warts and cancer) infections with sperm quality, oxidative stress, and inflammation in the male urogenital tract.

Study: Impact of high-risk and low-risk human papillomavirus infections on the male genital tract: effects on semen inflammation and sperm quality. Image Credit: wutzkohphoto/Shutterstock.com

Background 

HPV is a common sexually transmitted infection linked to cervical cancer in women. HPV types are classified as HR-HPV or LR-HPV based on their association with malignancies or benign genital warts, respectively.

While HPV in men has been less studied, recent research highlights its prevalence and potential effects on male reproductive health. HPV Deoxyribonucleic Acid (DNA) has been detected in various male genital specimens, but its impact on sperm quality and semen inflammation remains unclear.

Further research is needed to clarify the inconsistent findings on HPV’s impact on male reproductive health and better understand its role in sperm quality and semen inflammation.

About the study 

The present cross-sectional study enrolled 205 adult males attending a urology and andrology clinic between 2018 and 2021. Participants were males aged 18 years or older, undergoing semen analysis either as part of an initial fertility assessment due to lower urinary tract symptoms or as a routine control without infertility complaints.

Exclusion criteria included prior HPV vaccination, vasectomy ( a surgical procedure for male sterilization by cutting the vas deferens), azoospermia (a condition where a man has no sperm in his semen), significant varicocele (an enlargement of veins within the scrotum that can affect fertility), exposure to environmental pollutants, alcohol, drug, or marijuana use, recent fever, or antibiotic treatment.

The study adhered to the ethical standards of the Declaration of Helsinki and relevant Argentinian legislation. Informed consent was obtained from all participants. Subjects were divided into three groups: controls (negative for uropathogens and without leukocytopenia (the presence of a high number of white blood cells in semen, indicating inflammation or infection)), LR-HPV patients (positive for low oncogenic risk HPV genotypes), and HR-HPV patients (positive for high oncogenic risk HPV genotypes).

Semen samples were collected following specific hygiene instructions and analyzed within an hour of collection. HPV and other uropathogens were detected using polymerase chain reaction (PCR), with HPV genotyping performed through PCR-Restriction Fragment Length Polymorphism (RFLP).

Semen quality was assessed according to World Health Organization (WHO) guidelines, and sperm apoptosis/necrosis, cytokine levels, leukocyte subsets, and reactive oxygen species production were measured using flow cytometry and Enzyme-Linked Immunosorbent Assay (ELISA). Statistical analyses were conducted using GraphPad Prism and SPSS, with significance set at p < 0.05.

Study results 

In the study, 205 male participants with a median age of 35 years were enrolled, and out of these, 19% were found to be HPV-positive, indicating a high prevalence of the infection.

HPV genotyping was successful in 27 of the 39 positive cases, revealing that single HPV genotype infections were predominant, with multiple infections detected in only a small percentage of cases. Among the identified genotypes, HR-HPV types were the most common, particularly HPV-16, which was found in 59.2% of cases. LR-HPV genotypes were also present but less frequently.

To assess the potential impact of HR-HPV and LR-HPV on male fertility, the study analyzed sperm quality and apoptosis/necrosis in infected patients compared to controls. Routine sperm parameters showed no significant differences between controls and those infected with either HR-HPV or LR-HPV.

However, HR-HPV infections were associated with higher levels of sperm necrosis and increased production of reactive oxygen species (ROS), suggesting oxidative stress in these patients.

Interestingly, HR-HPV infections also led to reduced leukocyte counts and lower levels of inflammatory cytokines like interleukin (IL)-6 and IL-1β in semen, contrary to expectations.

The study further examined the role of co-infections with other uropathogens in HR-HPV-positive patients. While co-infections did not significantly alter conventional sperm quality parameters, they did exacerbate sperm necrosis and ROS production. Despite these effects, semen inflammation remained minimal, with reduced levels of Cluster of Differentiation (CD)45+ leukocytes observed in co-infected individuals. 

Conclusions

To summarize, this study examined HPV infections in men attending a urology clinic, highlighting the significant prevalence of HR-HPV genotypes, particularly HPV-16.

While routine semen parameters were unaffected, HR-HPV was linked to increased sperm necrosis, elevated ROS, and reduced inflammatory cytokines, indicating a local immunosuppressive environment.

These findings suggest that identifying HPV genotypes in men is crucial, as HR-HPV can disrupt immune responses and impact reproductive health, potentially facilitating viral persistence and transmission.