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Scientists have long questioned whether human papillomavirus, or HPV, infections in men could affect their sperm health and fertility. Now, an early study finds that high-risk HPV infections might be linked with slightly increased levels of sperm death.
Infections with high-risk strains of HPV appear to be associated with “significantly higher levels” of dead sperm cells than infections with low-risk strains, according to a small study published Friday in the journal Frontiers in Cellular and Infection Microbiology.
The higher rates of sperm death could be partially due to increased oxidative stress in sperm, which can result in DNA damage or impaired function.
“Previous studies have shown that HPV infections can impact sperm function. However, very few have investigated the differential effects of low-risk versus high-risk HPV genotypes,” Dr. Virginia Rivero, a professor at the Universidad Nacional de Córdoba in Argentina and the senior author of the new study, said in an email.
HPV includes a group of more than 150 viruses that are spread primarily through sexual contact, and it’s estimated that about 80% of people will have an HPV infection in their lifetime in the United States.
In most cases, HPV clears on its own within two years, but when infections don’t go away, health problems may occur. Low-risk strains most often cause warts, and high-risk strains have been associated with an increased risk of certain cancers, such as cervical, anal, penile and oropharyngeal cancers.
Rivero and her colleagues examined data on 205 adult men who provided semen samples at an urology clinic in Argentinabetween 2018 and 2021. None of the men had been vaccinated against HPV.
The researchers found that HPV was detected in 39 (19%) of the samples, with high-risk infections being more prevalent. The high-risk strain HPV 16 was the most frequent strain identified, found in 16 samples.
The researchers organized the samples into three groups: no HPV or 11 other urologic infections detected, high-risk HPV detected, and low-risk HPV detected. They then took a close look at the quality of the sperm in each group, performing a semen analysis at least twice for each sample.
Their analysis showed no association between HPV infection and a reduction in the standard markers used to evaluate semen quality, such as sperm concentration or sperm motility, meaning the way sperm move to their destination. But the samples from men with high-risk HPV infections had 2½ times more sperm death than those with low-risk infections, Rivero said.
The researchers also found that the samples with high-risk HPV infections showed higher levels of markers of cell stress compared with the low-risk HPV infection samples and the samples in which no HPV was detected. The samples with high-risk HPV infections also appeared to have lower counts of white blood cells, or leukocytes, which are important components of the body’s immune system.
“High-risk HPV types have a more detrimental effect on sperm and also create a local immunosuppressive environment, which may further facilitate the presence of co-infections,” Rivero said, adding that these findings suggest there could be benefit in testing men for HPV.
Most women usually are tested for HPV during routine Pap exams when screening for cervical cancer, but in the United States, HPV tests are not recommended to screen men, and there is no screening for men approved by the US Food and Drug Administration.
“In clinical practice urologists typically do not request HPV testing in men, and even less commonly do they request genotype testing to determine whether it is a high-risk or low-risk type,” Rivero said. “However, our findings suggest that it would be very beneficial to determine whether the HPV strain is high-risk.”
The study contributes to the body of research on HPV in men, but the findings are no reason for couples wanting to get pregnant to worry, said Dr. Bobby Najari, a urologist at NYU Langone Health in New York, who was not involved in the new study.
For instance, among heterosexual couples, if the female partner tests positive for high-risk HPV, that can indicate that the male partner probably has it too – but Najari said that couples shouldn’t panic.
“There was a significant increase in the number of dying sperm in men with high-risk HPV, but overall, the number of necrotic sperm, or dying sperm, was relatively low across all men, including the ones with high-risk HPV,” he said. “I also just don’t think that those sperm are the sperm that are contributing to pregnancy, whether that’s natural pregnancy or when we’re doing assisted reproductive technology. Sperm that are dying are not the sperm that are vigorously swimming and making that trek to fertilize the egg. And in the lab, these sperm are not the healthy, vigorously moving sperm that we’re selecting for fertilizing an egg when we’re doing assisted reproductive technology.
“If anything, I find it reassuring that the most important indicators of male reproductive potential – sperm count and sperm motility – were similar between men with high-risk HPV infections and other men,” Najari said. “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 exacerbate an already bad situation. Unfortunately, there are no clinically available ways to diagnose HPV infection in men outside of visible signs of warts or penile cancer.”
The study seems to raise more questions than answers, as it suggests that broader research on HPV in men could help parse whether high-risk HPV infections may affect fertility and pregnancy outcomes – and to what extent, said Dr. Janet Choi, a reproductive endocrinologist and ob-gyn who serves as the chief medical officer of the fertility and women’s health benefits company Progyny.
“While the researchers found no overall semen abnormalities linked to HPV, they did observe that men with high-risk HPV had more dead sperm. Dead sperm potentially indicates increased DNA fragmentation, a factor associated with infertility and miscarriages in other studies,” Choi, who was not involved in the new study, said in an email.
“A useful follow-up study could compare males dealing with infertility and abnormal semen to those with normal semen, alongside partners with infertility unrelated to the males,” she said. “Studying the prevalence of HPV in these different groups would help clarify the link, as previous research has shown a prevalence of detectable HPV in males with male infertility and abnormal semen, suggesting at least an association, if not a potential link, between the two.”
Some studies have suggested that HPV can affect cellular components of semen and could impair sperm count, motility, integrity, morphology and concentration, leading to effects on fertility. But others have shown no statistical difference in sperm concentration among HPV-negative and HPV-positive semen samples, nor have they demonstrated a role forHPV infection in male infertility.
Overall, the clinical significance of the new study – and what it means for fertility – is still not clear, said Dr. Ashley Lipps, an infectious disease doctor with The Ohio State University Wexner Medical Center, who was not involved in the new research.
“This study did not evaluate whether these differences actually lead to a significant reduction in male fertility. The main limitation of this study is a very small sample size - out of the 205 men who were evaluated in the study, HPV was only detected in 39 samples,” Lipps wrote in an email.
“Bottom line - interesting study but data is very preliminary. Additional larger studies are needed to further assess this impact of HPV infection on male fertility,” she said. “If someone is concerned about fertility problems it is best to speak with your healthcare provider for assessment. It is important to note that HPV is preventable- there is a vaccine available.”
Although there is no treatment for HPV, a vaccine can help prevent infections.
“Infection with high-risk HPV is entirely preventable through vaccination. So if parents want to do everything conceivable to optimize their chances at having grandchildren, they should ensure their boys are fully vaccinated for HPV at an appropriate age,” Najari said.
The CDC recommends two doses of the HPV vaccine for boys and girls ages 11 and 12. The first dose is recommended around those ages, and the second is recommended six to 12 months after the first dose. Children who start the vaccine series on or after their 15th birthday need three shots over six months. Vaccination is not recommended for people older than 26.
The rate of HPV vaccinations among US teens has not increased since the Covid-19 pandemic, according to a CDC report released Thursday, and there has been a decline in how many children are up to date on their HPV vaccine by age 13 among those born in 2010, compared with those born in 2007.
From 2015 through 2023, an estimated 52.9% of adolescents born in 2007 were up to date on their HPV vaccination by age 13, compared with 45.8% of those born in 2010, according to the report.
This suggests that among those born in 2010, coverage by age 13 was similar to pre-pandemic coverage levels, but the percentage of those who were up to date was 7.1 points lower than among the generation born in 2007.
“HPV vaccination is essential to prevent HPV-attributable cancers,” the CDC researchers wrote. “Although HPV vaccine initiation by birth year has returned to pre-pandemic levels, further efforts are needed to increase HPV vaccination coverage.”
Other ways to protect against HPV include using condoms during sex or, for women, getting tested for the virus during routine Pap exams.