Over the years, I have taught my residents and fellows that, if something does not make sense in clinical practice, it is probably wrong.
That maxim seems to apply in our approach to the preventive management of HPV.
HPV has rapidly assumed much greater prominence in the domains of infectious disease and oncology in the past couple of decades, especially since the recognition that several subtypes are associated with the genesis of cancers of the cervix, vulva, vagina, anus, penis, larynx and oropharynx.
More than 40,000 HPV–associated cancers are diagnosed each year in the United States. HPV is one of the most common sexually transmitted disorders worldwide, and it has been suggested that nearly all sexually active adults will harbor HPV at some time.
Fortunately, not all HPV subtypes are oncogenic. Antibodies are now available that are directed against the high-risk HPV subtypes — 6, 11, 16, 18, 31, 33, 45, 52 and 58 — which allow prevalence testing in large community samples.
Han and colleagues estimated that the overall genital HPV prevalence from self-collected penile swabs among men aged 18 to 59 years in the National Health and Nutrition Examination Survey was 45.2%. The researchers determined that 25.1% of study participants had positive testing for at least one high-risk subtype.
Another study by Rahman and colleagues showed 28.3% of men were seropositive for at least one of the 9-valent HPV subtypes. A study by Conway and colleagues of oral prevalence — based on gargle/rinse samples — showed an HPV prevalence of 5.5%.
We also know vaccination of children, adolescents and young adults reduces the prevalence of all types of HPV, but particularly the 9-valent cluster. Further, quadrivalent HPV vaccination induces HPV–specific antibodies in the oral cavity and serum of adults, although it is not yet clear whether these levels are sufficiently high to exert antiviral effects.
There also are data to show that quadrivalent HPV vaccine is effective against high-grade cervical lesions in 22% of individuals aged 20 to 29 years, although at a much lower rate than in those vaccinated when younger than 17 years. That said, others have demonstrated no major difference in induction of antibodies between men aged 27 to 45 years compared with a younger cohort.
Two studies have demonstrated antiviral antibody induction in women aged 36 to 45 years and an older cohort, with documentation of regression of cervical intraepithelial neoplasia in many of these patients.
Another very interesting aspect of this conundrum is the apparent induction of herd immunity. In other words, in a study by Chow and colleagues, the HPV–positivity rate of men who were sexual partners of vaccinated women was much lower than those consorting with unvaccinated females, implying the induction of herd immunity. In parallel, there also must be “natural” immunity, as there is no direct correlation between HPV expression between sexual partners.
Vaccination for older adults
So, where does this leave us?
We know that vaccination with quadrivalent HPV vaccine is apparently most effective the younger the patient. The FDA approval is specifically for patients aged younger than 26 years, and various recommendations focus on vaccination of females — and now males — in younger teenage years. Part of the argument is that exposure is likely to be less at that age, thus allowing the vaccine to exert its fully protective effect.
However, the studies cited above suggest that some measure of antibody induction is possible in much older age groups, and that these antibodies actually have a biological impact on viral expression and sometimes early cervix lesions. Skinner and colleagues reported 2 years ago, in the ongoing VIVIANE trial, that there is significant antiviral activity and activity against cervical abnormalities in women aged older than 25 years.