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When a male patient with genital warts asks whether recurrences will continue, you may find yourself delivering some sobering news.

Results from an analysis nested within the prospective, multinational Human Papillomavirus (HPV) Infection in Men (HIM) study shows that 44% of unvaccinated men ages 18 to 70 years in the U.S., Mexico, and Brazil carry a high burden of genital warts and can experience multiple recurrences that continue into old age.

Over a median followup of 50.4 months, 125 men (22%) with two or more genital warts "events" were at highest risk of recurrence. A total of 37 (6.5%) experienced up to 10 recurrences 16 weeks or more after the previous episode.

The highest proportion of genital wart recurrence was seen in U.S. men (53.3%), according to Anna R. Giuliano, PhD, founding director of the Center for Infection Research in Cancer (CIRC), at Moffitt Cancer Center, in Tampa, Florida, and colleagues.

Compared to men with genital warts in Brazil and Mexico, U.S. men also had the highest incidence of four or more recurrences (9.7% vs 2.3% and 6.3%, respectively), the researchers reported online in the .

Notably, the incidence rate of each subsequent episode of genital warts increased as the number of recurrences increased. The incidence of the first subsequent event was 13.1 per 1000 person-months. By the fourth recurrence, however, the incidence of genital warts recurrence had tripled to 36.6 per 1000 person-months.

The study also showed that the proportion of genital warts among HPV-6 and/or -11-positive men remained constant across events, and that 63% to 69% were positive for one or more of the 9-valent HPV vaccine types.

"HPV types 6 and 11 are the most frequently detected types in genital warts," the study authors noted. "What is unclear," they added, "is whether recurrence of an event with the same HPV type and anatomic location represents treatment failure or reacquisition of the same HPV type and progression to a new genital wart episode."

In the U.S., about $200 million is spent annually for "genital wart , which is often ineffective," they pointed out.

"The only way to shut this down is with gender-neutral prophylactic HPV vaccination," Giuliano told the Reading Room.

For vaccination to be effective at the population level in the U.S., she added, "we need to have at least 80% of boys and girls vaccinated." Currently, in the U.S. population sits below 50% (approximately 42% of girls and 28% of boys in the recommended age groups).

"We have to make sure that the general population understands the importance of having their children vaccinated and that every age-eligible patient receives a strong recommendation from their provider for HPV vaccination," Guiliano emphasized.

The American College of Obstetricians and Gynecologists (ACOG) and the U.S. Centers for Disease Control and Prevention (CDC) recommend for females and males ages 9-26 years, she said, noting that licensure extends to age 45 for both men and women.

Persistent HPV infection is the most common sexually transmitted infection , the investigators pointed out. It is associated with an increased risk of penile, oropharyngeal, and anal cancer in men, and an increased risk of cervical, vulvar, anal, and oropharyngeal cancer in women.

Studies from Australia, , and the U.S. show dramatic declines in genital wart prevalence following the roll-out of HPV vaccination programs, they noted.

"As genital warts are lesions associated with high rates of , vaccination of males against HPV represents an important public health strategy to reduce the large burden of in men as well as among their sexual partners," the study authors wrote.

In 2014, the HIM investigators published showing that men had a higher cumulative probability than women of acquiring HPV, regardless of age. Men also had higher rates of reinfection and reactivation of infections than their female counterparts. The HIM research group reported in 2017 that, in all countries studied, the incidence and prevalence of genital HPV infection in men remained constant over time, even in those middle-age and older.

In a accompanying the 2019 HIM study, Marc Steben, MD, of the Institut National de Santé Publique du Québec, and the Université de Montreal in Montreal, Quebec, Canada, said these results make "the case that we need sex-neutral vaccination programs to better protect men against HPV infection not only because of the risk of cancer but also because of the risk of GWs [genital warts]."

Steben noted that in British Columbia, the annual cost associated with low-risk HPV-6 and HPV-11 infections has been estimated to be 18% of the cost of all HPV-related diseases.

"GWs involve a huge proportion of the HPV burden, and since treatment does not prevent recurrences, we need to emphasize that 4-valent and 9-valent HPV prophylactic vaccines are safe and effective against GWs and remain effective for >10 years after vaccination," the editorialist wrote. "Although these vaccines may not have a therapeutic effect against GWs, they may act as an adjuvant to existing therapies for the prevention of recurrences."

Limits for Treating Asymptomatic Bacteriuria

A 2019 clinical practice guideline update on the management of asymptomatic bacteriuria has confirmed that there are only a limited number of populations in whom screening and antimicrobial treatment should be considered. Results from an expert review of the evidence published since the 2005 clinical practice guideline demonstrate that these populations include pregnant women and individuals undergoing invasive urologic procedures.

For other groups, treatment of asymptomatic bacteriuria is not beneficial, according to Lindsay E. Nicolle, MD, professor emeritus in the School of Medicine at the University of Manitoba, in Winnipeg, Manitoba, Canada, and other members of the expert panel.

Treatment of asymptomatic bacteriuria in these groups may be associated with substantial harms, including the development of antimicrobial resistance, C. difficile infection, and adverse antimicrobial effects, they reported online in .

"Inappropriate treatment of asymptomatic bacteriuria is a major contribution to inappropriate antimicrobial use," Nicolle told the Reading Room. "Addressing this issue should be a priority for antimicrobial stewardship programs."

Although there are no changes to the 2005 recommendations, the 2019 update includes a number of important populations not considered in the earlier guideline, Nicolle pointed out. These groups include children, solid organ transplant recipients, patients with neutropenia, and patients undergoing elective non-urologic surgery.

"For all of these groups, we found no evidence of benefit with treatment, so recommendations not to screen or treat were made," said Nicolle.

In addition, the panel looked at issues affecting populations with a high prevalence of asymptomatic bacteriuria, such as patients with a spinal cord injury and adults age 65 years and older.

Although the evidence was limited, it did not support the use of non-localizing clinical signs and symptoms, such as increased confusion and falls to ascertain symptoms of infection, said Nicolle. She added that "alternate diagnoses rather than urinary tract infection should be considered."