Authors: Jennifer A. Groner1, George D. Harris2 and Diane M. Harper3,4,5
TO THE EDITOR—The recent Centers for Disease Control and Prevention (CDC) study by Markowitz et al  provides limited and inconclusive data on 111 sexually active females between 14 and 19 years of age who received at least 1 dose of quadrivalent human papillomavirus vaccine (HPV4). The broad ranging conclusions are inconsistent with current knowledge about risk factors for HPV infection and HPV prevalence among US adolescents, herd immunity, and vaccine efficacy evaluation with fewer than 3 doses.
The single most important risk factor for HPV infection, after human immunodeficiency virus (HIV) infection, is number of lifetime sexual partners . Markowitz’s study aligns with this knowledge by showing for the 2007–2010 (postvaccination) time frame, a 4-fold increase in HPV prevalence among sexually active 14–19-year olds who have 3 or more lifetime sexual partners compared to those with fewer than 3 partners.
However, the study reports an adolescent cohort composed of twice as many adolescents who are both unvaccinated and minimally sexually active (hence, likely to have a low prevalence of HPV infection) as are vaccinated and highly sexually active. Combining these 2 groups lowers the overall reported postvaccination HPV prevalence leading to the false conclusion that vaccination lowered the HPV prevalence rates.
Reducing sexual activity is a potent prevention strategy for reducing HPV prevalence. Another recent CDC report indicates that 73% of 15–17 year-old females in the postvaccination era have not initiated sexual activity . Indeed, condom use is also proven to reduce HPV infection rates. Other significant successes reported by the CDC among adolescents in this same postvaccination time frame include an increased use of condoms, a decrease in the overall number of sexual partners during adolescence, and a large decrease in the number of teenage pregnancies [4,5].
In addition, adolescent sexual mating has been defined as an assortative mixing pattern, where males are twice as likely to be cutpoints as females . This means that vaccination of males, not females, is more likely to interrupt HPV transmission (and provide herd immunity) among females in the short term. Herd immunity is an unlikely scenario as the proportion of males receiving 3 HPV4 doses in the United States is reported to be only 6% . Therefore, the decrease in HPV prevalence reported in the Markowitz study is less likely due to HPV vaccination than due to adolescent sexual behavioral changes.
Similarly there are inconsistencies in the prevaccination HPV prevalence reported by Markowitz. Prevalence of any HPV type during the prevaccination time frame 2003–2004 among 14–19-year-old adolescents is reported by the same group of researchers  and does not differ from the postvaccination rates contrary to what was reported in Markowitz’s study (Table 1). The 2003–2004 prevaccination cohort includes 652 adolescents 14–19 years old. The prevalence of any HPV among those sexually active was 39.6%; this rate significantly falls to 24.5% when adolescents who report no sexual activity are included.