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Human Papillomavirus (HPV) Genotype 84 Infection of the Male Genitalia: Further Evidence for HPV Tissue Tropism? CORRESPONDENCE
  The Journal of Infectious Diseases March 1, 2008;197:776-778
Financial support: National Cancer Institute, National Institutes of Health (intramural research grant).
Reprints or correspondence: Dr. Philip E. Castle, Div. of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd., Rm. 5004, EPS MSC 7234, Bethesda, MD 20892-7234 (
To the Editor-Recent reports on human papillomavirus (HPV) infection in men from studies in Seattle, Washington [1], and in Tampa, Florida, and Tucson, Arizona [2, 3], have contributed significantly to the general knowledge of HPV epidemiology. Specifically, these studies both show in men that increased lifetime numbers of sex partners and smoking were associated with being [3] or becoming [1] HPV positive; that condoms may protect against HPV infection [3], as previously shown [4]; and that penile shaft, glans penis, and scrotum are the most commonly infected genital sites [1, 2]. Secondarily, these studies may have provided further evidence for genital HPV genotype-specific tissue tropism.
Previous studies have uniformly found that HPV genotype 16 (HPV-16) may be the most common HPV genotype detected in male genital specimens, and a similar finding has been observed in epithelial specimens from the cervix, vagina, and oral cavity. On closer inspection, surprisingly, several studies involving men from culturally and geographically diverse regions have now found the prevalence of HPV genotype 84 (HPV-84) infection to be similar to or greater than that of HPV-16 infection among male genital skin specimens [1, 5-8]. HPV-84 was also more commonly detected than HPV-16 or any other HPV genotype in persons with incident HPV infection [1]. To highlight these differences, the prevalence (and incidence) of HPV-84 infection was compared with the prevalence of HPV-16 infection in the genital skin of men (table 1). These patterns were also compared to prevalence patterns observed in the vagina and cervix. As shown, HPV-84 infections were equally or more commonly detected than HPV-16 infections in male genital specimens in all studies, whereas HPV-16 infections were more commonly detected than HPV-84 infections in cervical and vaginal specimens.
Table 1. Rates of infection due to 3 common genital human papillomavirus (HPV) genotypes, by genital site, reported in select studies.


Note. Studies measured the prevalence of HPV infection, unless otherwise indicated. Data in bold indicate the genotype associated with the highest rate of infection. LBA, line blot assay.
aIncluded are studies that detected HPV-84 by means of a polymerase chain reaction (PCR) assay that used PGMY09/11 or related primers that amplify HPV-84 efficiently. Few other studies have analyzed the rate of HPV infection due to genotype 84 because PCR primers (e.g., GP5+/6+) that rarely detect HPV-84 in men or women were used, suggesting perhaps that these primers do not efficiently amplify HPV-84.
bThis study measured the genotype-specific incidence of HPV infection.
cSelf-collection of cervicovaginal specimens.
The detection of HPV-84 and HPV-16 at these 3 sites were also compared to the detection of HPV genotype 61 (HPV-61), which, similar to HPV-84, is found in the 3 phylogenetic species, a group of genetically related genotypes that appear to preferentially infect the vagina (rather than the cervix) [10, 11, 14, 15]. However, the tissue-specific prevalence of infection with HPV-61, a prototypical vaginal genotype, and infection with HPV-84 differ still, and both differ from that of HPV-16 infection.
HPV tissue tropism is not without precedent. For example, HPV genotypes that cause warts vary by skin site [16]. HPV genotype 6, HPV genotype 11, and related genotypes cause genital warts (condyloma acuminata) and can infect the genital mucosa, causing low-grade lesions. HPV genotype 1 and related genotypes cause plantar warts, which are distinct from HPV genotype 2 and related genotypes that cause common skin warts. HPV genotype 7 preferentially causes butcher's warts.
Does HPV-84 preferentially infect male genital skin, and more generally, do groups of genital HPV types prefer different tissues? Further epidemiologic studies are needed to verify relationships of tissue specificity, HPV genotypes, and phylogenetic characteristics. Since the hypothesized tropisms are preferences rather than absolute requirements for specific anatomical sites, studies involving large populations of men and women that use broad-spectrum HPV genotyping assays are needed to confirm these patterns and account for the impact of age and sexual behaviors. Biologically, it is uncertain whether these variations in genotype-specific prevalence by anatomical site are the result of differences in susceptibility to infection, the ability of the tissue to sustain the infection at sufficiently high viral loads for detection, or some combination of both.
It is increasingly apparent that groups of phylogenetically related genital HPV genotypes have evolved multiple strategies for viral propagation, which are related, insofar as all are tied to epithelial differentiation. However, these strategies may differ, as is evident by differences in the type of anatomic tissue they preferentially infect. The molecular underpinnings of these viral survival strategies (i.e., the viral genetic determinants and their interaction with the host), are not well understood and remain an important inquiry for understanding the pathobiological characteristics of HPV infection. Most infection strategies are benign and have little or no clinical import, whereas a few, unfortunately, can cause cancer, primarily of the cervix. Greater insight into these differences could shed light on the mechanism(s) of HPV-induced carcinogenesis.
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Philip E. Castle
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
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