Concordance of Human Papillomavirus (HPV) Type between Sex Partners: Implications for Effective Utilization of an HPV Vaccine

Defining the biology and dynamics of human papillomavirus (HPV) transmission between sex partners has remained elusive. Over the past few decades, landmark advances in biotechnology have given birth to the field of molecular epidemiology, which has allowed a clearer picture of the complex dynamics of many viral diseases, including HIV infection, influenza, infection with avian viruses, and HPV infection [1–4]. Clearly, defining the transmission dynamics of HPV may influence public health decisions regarding where the greatest benefit of immunization against HPV can be realized.

In this issue of Clinical Infectious Diseases, Bleeker et al. [5] investigate the distribution and concordance of type-specific genital HPV infection among 238 heterosexual couples in which the woman had documented cytologic or histologic evidence of cervical dysplasia. At baseline, the majority of women and men in this study shed at least 1 of the 45 HPV types included in the assay, and >80% of subjects tested positive for at least 1 high—oncogenic-risk (HR) HPV type. The authors report a marked concordance of type-specific HPV between heterosexual partners, notably involving several HR HPV types, as well as low—oncogenic-risk (LR) HPV type 11.

Bleeker et al. [5] also determined HPV loads for HR HPV types 16, 18, 31, and 33 in subjects who tested qualitatively positive for these types. There was an association between HPV-16 load and type-specific concordance between couples. In the women, there was a significant association between HPV load and type-specific concordance with their partners for each of the HR types 16, 18, 31, and 33. The same was true for the HPV loads in the male partners in the case of HPV-16; however, this association could not be determined for HPV types 18, 31, and 33 because of the high proportion of samples that were below the detection level of the assay.

At this point, it is worthwhile to remind ourselves of the population under study: all of the female partners had some form of cervical dysplasia noted by pathologic examination. Although Bleeker et al. [5] do not report the relative proportions of low-grade vs. high-grade cervical squamous intraepithelial lesions (SILs) in the women who met criteria for inclusion in the analysis, this detail may not be particularly germane with regard to the authors' overall conclusions. In fact, the majority of low-grade cervical SILs harbor HR HPV types in nonintegrated episomal forms [6]. Because HR HPV types constitute the majority of genital HPV carriage in the general population, a result of low-grade dysplasia could be regarded as a potentially transitory state to high-grade dysplasia in persons who test positive for HR HPV types. The mystery remains as to what the best predictor is for progression from low-grade to high-grade SILs, which would open up the possibility for targeted prevention.

At this time, several HPV vaccines are in various stages of development [7]. Although the indications for HPV vaccine in the US population remain to be determined, the initial focus has been on use of the vaccine as a tool for prevention of acquisition of HPV infection early in life [8]. However, another clinical indication for vaccines against chronic viral infections is emerging: that of an immunity-boosting therapy for the chronically infected host, aimed at preventing both the end-stage consequences and the clinical recurrences of the infection targeted by the vaccine [9–11]. Taken together with previous data published by Bleeker and colleagues that revealed a high prevalence of squamous intraepithelial lesions of penile skin in the sex partners of women with cervical SILs [12], does the present study imply that genital HPV infection is another sexually transmitted disease for which “treatment of the partner” should be considered? Early-phase studies of some HPV vaccines suggest that they could be effective immunomodulators in chronically infected hosts by inducing regression of high-grade SILs without ablative intervention [13]. Whether some vaccines may be effective immunomodulators to prevent the clinical manifestations of their targeted chronic viral infections is a subject of intense interest.

Bleeker et al. [3] have effectively implicated the importance of the sex partner in the viral dynamics of HR HPV infection of the genital tract. This information may be very useful when we eventually have access to the clinical tools to prevent HPV acquisition early in life. Careful consideration should be given to preventive vaccination of persons of both sexes, to break the transmission cycle of HR HPV types within the sexually active population.

Acknowledgments

Potential conflicts of interest. L.A.P.: no conflicts.