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Scientists have long wondered whether human papillomavirus (HPV) infection in men affects sperm health and fertility. Now, early research has found that high-risk HPV infection may be associated with a small increase in sperm death.
Infection with high-risk HPV strains appears to be associated with “significantly higher levels” of dead sperm cells than infection with low-risk strains, according to a small study published Friday in the journal Frontiers in Cellular and Infectious Microbiology.
The high sperm mortality rate may be due in part to increased oxidative stress in sperm, which can result in DNA damage and impaired function.
“Previous studies have shown that HPV infection can affect sperm function, but few studies have investigated the differential effects of low-risk and high-risk HPV genotypes,” Virginia Rivero, PhD, a professor at the National University of Córdoba in Argentina and senior author of the new study, said in an email.
HPV includes more than 150 different types of the virus that are spread primarily through sexual activity, and it is estimated that approximately 80% of people in the United States will be infected with HPV in their lifetime.
In most cases, HPV goes away on its own within two years, but if the infection doesn’t go away, it can cause health problems. Low-risk strains most often cause warts, while high-risk strains are associated with an increased risk of certain cancers, including cervical, anal, penile, and oropharyngeal cancer.
Rivero and his colleagues looked at data from 205 adult men who provided semen samples at urology clinics in Argentina between 2018 and 2021. None of the men had received the HPV vaccination.
The researchers found that HPV was detected in 39 (19%) of the samples, indicating a higher incidence of high-risk infections. The most common strain identified was the high-risk strain HPV16, which was found in 16 samples.
The researchers divided the samples into three groups: those without HPV or the other 11 urinary tract infections, those with high-risk HPV, and those with low-risk HPV. They then looked at the sperm quality of each group and performed at least two semen analyses on each sample.
Their analysis found no association between HPV infection and declines in standard measures used to assess semen quality, such as sperm concentration or sperm motility (how sperm travel to their destination). But samples from men with high-risk HPV infections were 2.5 times more likely to have dead sperm than those from men with low-risk infections, Rivero said.
The researchers also found that samples with high-risk HPV infection had higher levels of markers of cell stress compared with samples with low-risk HPV infection and samples with no detectable HPV. Samples with high-risk HPV infection also appeared to have lower numbers of white blood cells, a key component of the body’s immune system.
“High-risk HPV types may have a more adverse effect on sperm and create a local immunosuppressive environment, further facilitating coinfection,” Rivero said, adding that these findings suggest there may be benefit to HPV testing in men.
While most women are typically tested for HPV during routine Pap tests when they are screened for cervical cancer, HPV testing is not recommended for screening men in the United States, and there is no screen approved for men by the U.S. Food and Drug Administration.
“In clinical practice, urologists don’t typically require men to undergo HPV testing, and even less often they require genotyping to determine whether they have high-risk or low-risk types,” Rivero said. “However, our findings suggest that determining whether an HPV strain is high-risk could be of great benefit.”
The study contributes to research on HPV in men, but it’s not a reason for couples trying to conceive to worry, said Dr. Bobby Najari, a urologist at NYU Langone Health in New York, who was not involved in the new study.
For example, in a heterosexual couple, if the female partner tests positive for high-risk HPV, the male partner is probably also infected, but Najari said couples don’t need to panic.
“Although the number of dead sperm was significantly increased in men with high-risk HPV infection, overall, the number of necrotic, or dead, sperm was relatively low in all men, including those with high-risk HPV infection,” he said. “And we don’t believe those sperm are contributing to conception, either naturally or through assisted reproduction. Dead sperm are not the sperm that are swimming vigorously and making the journey to fertilize an egg. And in the lab, these sperm are not the healthy, vigorously motile sperm that we select to fertilize an egg in assisted reproduction.”
“It is rather reassuring that sperm count and sperm motility, the most important indicators of male fertility, were similar in men with high-risk HPV infection and other men,” Najari said. “I can imagine that the main scenario in which this study concerns men whose sperm production is already severely impaired. I am concerned that this study could make high-risk HPV infections even worse in an already bad situation. Unfortunately, there is no way to clinically diagnose HPV infection in men other than the visible signs of warts or penile cancer.”
The study appears to raise more questions than it answers, said Dr. Janet Choi, a reproductive endocrinologist, obstetrician-gynecologist, and chief medical officer of fertility and women’s health benefits company Progyny, who suggests that more extensive research on HPV in men could help parse whether and to what extent high-risk HPV infections affect fertility and pregnancy outcomes.
“While the researchers did not find any overall semen abnormalities associated with HPV, they did observe that men with high-risk HPV had more dead sperm, which may indicate increased DNA fragmentation, a factor that has been linked to infertility and miscarriage in other studies,” Choi, who was not involved in the new study, said in an email.
“A useful follow-up study would compare men with infertility or abnormal spermatozoa to men with normal spermatozoa and to the infertile partners of men who are not related to the men,” she says. “Looking at the prevalence of HPV in these different groups would help clarify the association. Previous studies have shown detectable HPV prevalence in men with male infertility and abnormal spermatozoa, suggesting at least a potential association, if not a link, between the two.”
Some studies suggest that HPV may affect the cellular components of semen, reducing sperm count, motility, integrity, morphology, and concentration, potentially affecting fertility. However, other studies have not found a statistical difference in sperm concentration between HPV-negative and HPV-positive semen samples, nor have they demonstrated that HPV infection plays a role in male infertility.
Overall, the clinical relevance of the new study and what it might mean for fertility is still unclear, said Dr. Ashley Lips, an infectious disease specialist at Ohio State University Wexner Medical Center, who was not involved in the new study.
“The study did not evaluate whether these differences actually translate into a greater reduction in male fertility. The main limitation of the study is the very small sample size: of the 205 men evaluated in the study, only 39 samples had detectable HPV,” Lips said in an email.
“The bottom line is that while this is an interesting study, the data are still early and larger studies are needed to further evaluate the impact of HPV infection on male fertility,” she said. “Anyone who is concerned about fertility issues would be best off speaking to their health care provider to get evaluated. It’s important to remember that HPV is preventable and a vaccine is available.”
There is no cure for HPV, but a vaccine can help prevent infection.
“High-risk HPV infection is completely preventable through vaccination, so parents who want to do everything they can to maximize their chances of having grandchildren should have their sons fully vaccinated against HPV at the 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 given at these ages, with the second dose recommended 6 to 12 months after the first. Children who start vaccinating after their 15th birthday should get three doses over a 6-month period. Vaccination is not recommended for people over 26 years of age.
According to a report released Thursday by the CDC, HPV vaccination rates among U.S. teenagers have not increased since the COVID-19 pandemic, and fewer teenagers born in 2010 have completed the HPV vaccination by age 13 compared with those born in 2007.
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From 2015 to 2023, an estimated 52.9% of adolescents born in 2007 would have completed HPV vaccination by age 13, compared with 45.8% of adolescents born in 2010, according to the report.
This suggests that for those born in 2010, the rate of insurance coverage by age 13 was similar to pre-pandemic rates, but the proportion of people with up-to-date insurance was 7.1 percentage points lower than those born in 2007.
“HPV vaccination is essential to prevent HPV-related cancers,” the CDC researchers wrote. “Although HPV vaccination initiation by birth year has returned to pre-pandemic levels, further efforts are needed to increase HPV vaccination rates.”
Other ways to protect yourself from HPV include using condoms during sex and, for women, getting tested for the virus with regular Pap tests.
