Recent research hints at a potential link between high-risk HPV infections in males and elevated amounts of non-viable sperm cells.
High-risk HPV infections apparently lead to "substantially higher" incidences of deceased sperm cells compared to low-risk HPV strains, based on a small study published recently in the journal Frontiers in Cellular and Infection Microbiology.
This increased frequency of sperm death could potentially be attributed to enhanced oxidative stress within sperm, which can result in degradation of DNA or hindered function.
Previously, numerous studies have confirmed that HPV infections tend to impact sperm performance. However, relatively few investigations have explored the differential repercussions of low-risk versus high-risk HPV genotypes, stated Dr. Virginia Rivero, a professor at Universidad Nacional de Córdoba in Argentina and the study's lead author, in an email.
HPV includes a large group of over 150 viruses primarily transmitted through sexual contact. Approximately 80% of individuals in the United States are estimated to acquire an HPV infection during their lifetime.
In most instances, HPV dissipates naturally within two years. Nevertheless, if the infections persist, health complications may develop. Low-risk strains mostly manifest as warts, while high-risk strains have been connected to an enhanced risk of specific types of cancer, including cervical, anal, penile, and oropharyngeal cancers.
Rivero and her colleagues scrutinized data from 205 adult men who provided semen samples at an Argentinian urology clinic between 2018 and 2021. None of the men had been immunized against HPV.
HPV was detected in 39 (19%) of the samples, with high-risk infections more prevalent. The high-risk strain HPV 16 was the most common strain found, present in 16 samples.
The researchers divided the samples into three categories: no HPV or other urologic infections identified, high-risk HPV infections detected, and low-risk HPV infections detected. They then examined the sperm quality in each group through multiple semen analyses.
The analysis revealed no link between HPV infection and reductions in common indicators used to assess semen quality, such as sperm concentration or motility. However, samples from men with high-risk HPV infections exhibited 2.5 times more sperm death than those with low-risk infections, Rivero noted.
In addition, the samples with high-risk HPV infections demonstrated higher levels of cell stress markers compared to low-risk HPV infection samples and samples without HPV detection. Moreover, the high-risk HPV infection samples also showed lower leukocyte counts, which are essential components of the body's immune system.
“High-risk HPV types inflict greater harm on sperm and create a local immunosuppressive environment, which could further promote the presence of other infections,” Rivero cited, suggesting a potential advantage in evaluating men for HPV.
Generally, women undergo HPV testing during routine Pap exams to monitor for cervical cancer, but HPV tests are not recommended for men's screening in the United States, and no such screening method has been authorized by the US Food and Drug Administration.
“In clinical practice, urologists seldom request HPV testing for men, and genotype testing to distinguish high-risk and low-risk types is even less common,” Rivero noted. “However, our findings indicate that determining the HPV strain’s type would be highly beneficial.”
No need for panic among couples planning pregnancy
While the research adds to the existing body of knowledge on HPV in men, clinical implications for couples aiming for pregnancy should not be overstated, said Dr. Bobby Najari, a urologist at NYU Langone Health in New York, who was not associated with the new study.
For instance, if the female partner tests positive for high-risk HPV, it could suggest that the male partner is likely infected as well, but couples need not panic, Najari pointed out.
“There was a significant increase in the number of deceased sperm in men with high-risk HPV, but overall, the number of necrotic sperm, or deceased sperm, was relatively low across all men, including those with high-risk HPV,” he emphasized. “I also just don’t think that those sperm are the sperm contributing to pregnancy, whether that’s through natural pregnancy or assisted reproductive technology. Sperm that are dying are not the sperm that are vigorously swimming and making the journey to fertilize the egg.”
“If anything, I find it reassuring that the most crucial indicators of male reproductive potential – sperm count and sperm motility – were similar between men with high-risk HPV infections and other men,” Najari concluded. “The main scenario I can envision where this study is relevant is a man with already severely impaired sperm production. This study would make me concerned that a high-risk HPV infection would worsen an already negative situation. Unfortunately, there are no clinically available methods to diagnose HPV infection in men outside of visible signs of warts or penile cancer.”
The study appears to raise more questions than answers, suggesting that further investigation into HPV in men may help identify whether high-risk HPV infections impact fertility and pregnancy outcomes, and to what degree, added Dr. Janet Choi, a reproductive endocrinologist and ob-gyn serving as Progyny’s chief medical officer.
While the investigation discovered no widespread semen anomalies related to HPV, they noted that men with high-risk HPV tended to have a higher proportion of non-viable sperm. This could point towards increased DNA fragmentation, a factor linked to infertility and miscarriages in previous studies, as suggested by Choi, who wasn't involved in the study.
An intriguing progression would be to compare men dealing with infertility and anomalous semen with those having normal semen, along with their unrelated infertility-affected partners. This would help clarify the connection, as previous studies have shown a prevalence of detectable HPV in males with male infertility and abnormal semen, indicating at least an affiliation, if not a potential link, between the two.
Various studies have implicated HPV's impact on semen components and the possibility of affecting sperm count, motility, integrity, morphology, and concentration, potentially influencing fertility. However, other research has reported no statistical difference in sperm concentration between HPV-negative and HPV-positive semen samples and has failed to establish a role for HPV infection in male infertility.
The study's clinical relevance for fertility remains unclear, according to Dr. Lipps, an infectious disease expert from The Ohio State University Wexner Medical Center, who wasn't involved in the research.
"This research didn't determine if these differences result in a substantial reduction in male fertility. The study's primary limitation is its small sample size – out of the 205 men analyzed in the study, HPV was only detected in 39 samples," Lipps wrote in an email.
"Overall, the study's findings are preliminary. Further research with larger sample sizes is required to substantiate this impact of HPV infection on male fertility. If someone has concerns about fertility issues, it's advisable to consult with their healthcare provider for evaluation. It's essential to remember that HPV is preventable – a vaccine is available."
Reducing HPV Risk
Although HPV cannot be treated, a vaccine can prevent infections.
"HPV infections caused by high-risk strains can be entirely prevented through vaccination. If parents wish to improve their prospects of having grandchildren, they should ensure their sons are fully vaccinated against HPV at an appropriate age," Najari suggested.
The CDC advises two doses of the HPV vaccine for boys and girls aged 11 and 12. The first dose should be given around those ages, and the second dose should follow 6 to 12 months afterward. Boys and girls who commence the vaccine series after their 15th birthday require three doses administered over 6 months. Vaccination is not recommended for individuals older than 26.
Data from a CDC report released Thursday indicates that HPV vaccinations among US teens have not increased since the pandemic began, and there has been a decline in up-to-date HPV vaccination completion by age 13 among those born in 2010 compared to those born in 2007.
From 2015 to 2023, an estimated 52.9% of adolescents born in 2007 were up to date on their HPV vaccination by age 13, while 45.8% of those born in 2010 were up to date, according to the report.
This suggests that among those born in 2010, coverage by age 13 was similar to pre-pandemic levels, but the percentage of those who were up to date was 7.1 points lower than among the 2007 generation.
"HPV vaccination is vital in preventing HPV-related cancers," the CDC researchers said. "Although HPV vaccine initiation by birth year has returned to pre-pandemic levels, further efforts are needed to increase HPV vaccination coverage."
Additional methods to shield against HPV include utilizing condoms during intercourse or, for women, undergoing HPV tests during routine Pap exams.
The increased frequency of sperm death in men with high-risk HPV infections could negatively impact their reproductive health, as higher levels of cell stress markers and lower leukocyte counts were observed in these samples. Regular HPV vaccination can help prevent HPV infections, which are primarily transmitted through sexual contact, to reduce the risk of HPV-related health complications.
