European Urology

Giuliano AR, Palefsky JM, Goldstone S, et al
N Engl J Med 2011;364:401–11
Expert's summary:
In their original paper, Giuliano and coworkers report the results of an 18-country, randomized, placebo-controlled, double-blind study aimed at evaluating the efficacy of the quadrivalent human papillomavirus (HPV) vaccine against external genital lesions and anogenital infection in males aged 16–26 yr. Their findings showed that the vaccine promoted an efficacy of 65.5% in terms of external genital lesions (mostly condylomata acuminata) when considering the intent-to-treat population; moreover, the efficacy rate even increased up to 90.4% in the per-protocol population for lesions related to the four types of HPV specifically covered by the vaccine (ie, HPV 6, 11, 16, and 18). Although still very high, the efficacy was higher in heterosexual men as compared with individuals who had sex with male partners (92.4% vs 79%, respectively). Moreover, quadrivalent HPV vaccine promoted an overall reduction of 85.6% in persistent infection with HPV 6, 11, 16, or 18. Injection-site adverse events were significantly more frequent among those men who had received quadrivalent HPV vaccine as compared with those receiving placebo. Conversely, the rate of treatment-emergent systemic adverse events did not differ between groups, and no serious adverse events were eventually related to the vaccine.
Expert's comments:
Welcome, possibility of prevention! And I strongly emphasize that we need many more of these vaccines against several of the many risk factors that can do daily damage, undeterred, to the overall health of the individual and, more specifically, to men's sexual and reproductive health. Having an effective preventive method for men seems like a dream for all those clinicians/health professionals who are involved in taking care of men and/or couples with issues related to sexuality or reproductive difficulties. The prestigious manuscript by Giuliano et al provides several critical considerations with an interesting link to different aspects of the urologic, sexual, and reproductive medicine fields.
Human papillomavirus is not just a problem for females
Infection with HPV is highly prevalent in both genders, and anogenital HPV is the most common sexually transmitted infection worldwide [1] and [2]. Certainly, as urologists, we know that HPV infects the squamous epithelium in both sexes, potentially leading to anogenital warts, and that the lifetime risk of having HPV-related genital warts is approximately 10% in industrialized countries [3]. Likewise, we know that HPV can cause or facilitate up to 5.2% of all cancers in both genders, with a specific association of HPV DNA being reported in males to penile, anus, and head-and-neck cancers [4]. These data may seem obvious, but, unfortunately, with no offense intended to any urologist, I think they are not. We are not dealing with a super-rare medical condition with only specific subcohorts of the population involved.

I invite you all to carefully read the introduction of the manuscript by Giuliano and coworkers. They clearly summarize some clinical aspects of paramount importance: (1) The rate of genital HPV infection of men and women is similar; (2) conversely, there are differences between sexes concerning the immune response to HPV, with a greater proportion of HPV-seropositive females and higher antibody titers in females. The authors outline that the lower immune response to natural infection in males could at least partially explain the higher prevalence of HPV infections and the constant incidence and prevalence of HPV infection across a wide age range in males.

What does this mean at the end of the day? Males are at risk of HPV infection and, consequently, of all possible HPV-related sequelae for a much longer part of their lives. Both urologists and andrologists are the privileged physicians of males and, therefore, should well know how all male patients, at least those who are sexually active, deserve a careful and periodic examination of the external genitalia and the anal region. What better opportunity than during office visits?
We are not talking about a problem that affects only a few persons
Do not tell me that you have not thought at least once that HPV infection and acquisition solely concerned sexually uninhibited persons and men who have sex with men. To date ≥120 types of HPV have been identified, of which ≥30 are sexually transmitted. Certainly not all of them place patients at high oncogenic risk (ie, HPV 16 and 18) and not all infected individuals will necessarily develop anogenital warts, precancerous lesions, or cancer. However, the World Health Organization has clearly reported that between 9% and 13% of the world population has contracted the infection and that between 9% and 13% of those infections will continue in carcinomatous lesions, even in immunocompetent individuals. Think for a moment of only penile lesions: the annual number of males that develop penile cancer in the European Union is estimated at 3100, which is equivalent to an age-standardized rate of 12 per 1 million males [5].

Among the risk factors are age at first report, the number of sexual partners during the lifespan, and the frequency of intercourse. Cigarette smoking would seem to favor the persistence of HPV infection. Additionally, the condom does not seem protective, for not all areas of skin are adequately protected. Risk factors such as these should be discussed with men, young or old.

Some relative aspects were discussed in a recent manuscript by Gatta et al. [6]. As mentioned, penile cancer is usually considered rare. In this context, based on the RARECARE definition (incidence <6 per 100 000 per year), the estimated annual incidence of all rare cancers in Europe reaches about 108 per 100 000, corresponding to 541 000 new diagnoses annually or 22% of all cancer diagnoses. Five-year relative survival is, on average, worse for rare cancers (47%) than common cancers (65%). About 4.3 million patients are living today in the European Union with a diagnosis of a rare cancer; this is 24% of the total cancer prevalence. This makes me think: Welcome, quadrivalent vaccine for HPV!

Conflicts of interest

The author has nothing to disclose.