Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide. Persistent infection with certain types of HPV has been established as a necessary cause for cervical cancer1 2 and has been associated with cancer of the anus, vulva, vagina, penis, and oropharynx.3 4 Approximately 5.2% of all cancers worldwide are attributable to HPV infection.3 Moreover, the economic burden of HPV infection is high, and second only to the cost of HIV infection.5 Currently, there are two HPV vaccines licensed for use worldwide that have proven to be effective in preventing HPV infection and progressive disease in people who were previously HPV naïve.6 With widespread use, the vaccines could provide a cost-effective prevention strategy.

Antibody response to HPV infection is considered a key determinant of protective immunity and may play a role as a predictor of HPV-associated cervical neoplasia.2 7 The protective antibody response is mainly type-specific and directed against conformational epitopes of the major capsid protein L1,8 while antibodies to E6 and E7 oncoproteins may be markers of invasive cervical cancer, with tumour stage and mass determining the magnitude of the response.9 Seroconversion occurs several months after detection of HPV-DNA infection; approximately only 60% of women with an incident HPV-DNA infection seroconvert within 18 months after detection. No differences in median time of seroconversion are observed by HPV type, although antibody responses to high-risk HPV types have been found to persist longer.1 10 While HPV DNA testing detects current infection, serological testing serves as a useful epidemiological research tool to measure lifetime exposure to HPV infection because antibodies may persist even after the virus has cleared. Although HPV-16 is the most common HPV type detected in most regions of the world,11 no population-based seroepidemiological studies of HPV-16 infection have been conducted in Puerto Rico (PR). An estimate of natural HPV infection would not only help understand the burden of the disease, but also provide the necessary baseline data for HPV vaccine implementation and monitoring in PR. Hence, the purpose of this pilot study was to estimate prevalence of HPV-16 immunoglobulin G (IgG) responses and factors associated with HPV-16 seropositivity in a cross-section of adults in PR.

The first HPV vaccine, which includes HPV-16, was approved by the Food and Drug Administration (FDA) for use in the USA and PR in 2006 for women only (aged 9–26 years) and later in 2008 for men. Our estimate of HPV-16 seropositivity for this subsample of adults in PR (11.3%) from 2005 to 2008 is comparable to those reported in the USA (10.4%) for persons aged 14–59 years participating in the NHANES 2003–2004.17 Our findings are also comparable to those reported in studies worldwide. A study in the Netherlands during 2006–2007 among persons aged ≥14 years found an HPV-16 seroprevalence of 11.3%,11 whereas a study in England among persons aged 10–49 years reported a seroprevalence of 14.7%.18 Also, consistent with the study by Dunne et al,19 the prevalence of HPV seroreactivity in our study was higher among women (15.8%) than men (5.6%), with fourfold increased odds of infection. In a study performed by Stone et al,7 HPV-16 seroreactivity was over two times higher in women (17.9%) than in men (7.9%), and constant across all age and racial/ethnic groups evaluated in the study. Moreover, several studies have shown this sex difference in antibody response in all HPV vaccine types (6, 11, 16 and 18).17 18 Sex differences in HPV-16 seroreactivity are also observed among high-risk populations. Women attending sexually transmitted diseases clinics had higher prevalence of HPV-16 seropositivity (30.2%) than men (18.7%), supporting that there are biological reasons for men and women differing in serological responses.20 Potential explanations proposed by Thompson et al20 include that men may be: (1) not as susceptible to HPV-16 infection, (2) more able to clear the infection spontaneously without developing a systemic antibody response and (3) less likely to get infected with HPV-16 given that their sexual exposure frequently involves keratinised epithelium (penis) rather than mucosal epithelium (cervix).

In concordance with the literature, HPV-16 seropositivity was also associated with lifetime number of sexual partners, a strong predictor of HPV seropositivity for men and women.2 7 10 21 In a study performed in Costa Rica, it was found that women with at least three lifetime sexual partners had a twofold increase in the detection of HPV-16 antibodies compared with women with one lifetime sexual partner.22 Similarly, results from the HPV Infection in Men study showed that men with multiple lifetime male partners (≥11 partners) were more likely to be seropositive to HPV-16 (OR=7.74; 95% CI 3.96 to 15.12).10 We observed a strong association between smoking and HPV-16 seropositivity, with smokers being more likely to be positive for HPV-16 antibodies in this sample. Smoking habits have been identified as a risk factor for HPV infection and seropositivity, but these findings are inconsistent.17 23 24 Unlike previous studies showing a decline in seropositivity among those aged 50+ years, we did not observe a significant association between age and HPV-16 seropositivity.4 17 21 This could be due to the small numbers of seropositive persons in this study.

Study limitations include the lack of HPV vaccination data of participants and the sample size; only 51 samples were HPV positive, limiting the power of our study to detect significant associations with HPV serology. Future studies should evaluate HPV seroprevalence using a larger population-based sample; the research team is currently executing a population-based study among women living in the San Juan metropolitan area, which will soon produce data on this topic. All HPV serology assays are limited by the lack of commercial reagents and difficulties in comparing results between different platforms. We reported on results in terms of IU to help in interstudy comparisons.

This study is the first to evaluate the prevalence and correlates of HPV seroprevalence in PR. With the introduction of the two prophylactic HPV vaccines, it is important to establish baseline population HPV prevalence and better identify population subgroups at high risk for HPV-related cancers in the population before the uptake of the vaccine continues to increase. This is particularly important in PR, where population-based estimates of vaccine uptake are low among children and adults (<5% among women aged 16–26 years; 2010-2013 data).25 Knowledge of the burden of infection prior to the expansion of these programmes will allow a better assessment and understanding of the short-term and long-term effectiveness of this primary prevention strategy for anogenital lesions (cervix, vagina, vulva, and anus). Thus, these initial findings provide a much needed insight on the epidemiology of HPV infection in PR and will permit the expansion of future HPV-related research.