Human papillomavirus prevalence and type distribution in penile carcinoma. J Clin Pathol

Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Program, Institut Català d' Oncologia, IDIBELL, L' Hospitalet de Ll, Barcelona, Spain.
Journal of clinical pathology (Impact Factor: 2.92). 09/2009; 62(10):870-8. DOI: 10.1136/jcp.2008.063149
Source: PubMed


Penile carcinoma is an uncommon and potentially mutilating disease with a heterogeneous aetiology. Several risk factors have been established for its development. Human papillomavirus (HPV) infection seems to play an important role in the development of a subset of these carcinomas and its presence is thought to be related to the histological type. HPV prevalence in penile tumours is reported to be associated to a variety of morphological changes. Its determination will provide a better estimate for HPV related cancer burden and its preventable fraction.
A systematic and comprehensive literature review of the major penile cancer studies published from 1986 until June 2008 evaluating the HPV prevalence among the different histological types was carried out.
31 studies including 1466 penile carcinomas were reviewed. Global HPV prevalence was 46.9%. Relative contribution was: HPV-16 (60.23%), HPV-18 (13.35%), HPV-6/11 (8.13%), HPV-31 (1.16%), HPV-45 (1.16%), HPV-33 (0.97%), HPV-52 (0.58%), other types (2.47%). Assessment of multiple infections contribution is limited due to study design. Basaloid and warty squamous cell carcinomas were the most frequent HPV-related histological types, but keratinising and non-keratinising subtypes also showed prevalence rates of around 50%.
About half of the penile tumours were associated with HPV 16-18 with little presence of other genotypes. Research on the mechanisms behind penile carcinogenesis is warranted. Available HPV vaccines are likely to be effective in penile tumours.

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    • "Previous literature suggests that HPV DNA is detected in approximately half of penile cancers with variations between studies. HPV16 is the most common type detected, followed by HPV18 [5]. It remains unclear whether the differences in prevalence between studies reflect a real variation across populations or differences in sample selection or in the technology used. "
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    ABSTRACT: Background: Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia. Objective: To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16INK4a) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included. Design, setting, and participants: After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA-positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16INK4a expression, a surrogate marker of oncogenic HPV activity. Outcome measurements and statistical analysis: HPV DNA prevalence and type distributions were estimated. Results and limitations: HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2-36.1) and in 87.1% of HGSILs (95% CI, 78.0-93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16INK4a upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively. Conclusions: About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV activity marker, respectively. The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines in the reduction of HPV-related penile neoplastic lesions. Patient summary: About one-third to one-quarter of penile cancers were related to human papillomavirus (HPV). The observed HPV type distribution reinforces the potential benefit of current and new HPV vaccines to prevent HPV-related penile neoplastic lesions. About one-third to one-quarter of penile cancers were related to human papillomavirus (HPV) when considering HPV DNA detection alone or adding an HPV activity marker. The observed HPV type distribution reinforces the benefit of HPV vaccines in the reduction of HPV-related penile cancer.
    Full-text · Article · Jan 2016 · European Urology
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    • "Human papillomavirus (HPV) infection is a necessary element for the development of virtually all cases of cervical cancer in women [1], and has also been identified as a risk factor for the development of anal, penile, and oropharyngeal cancers [2-4]. In particular, oropharyngeal squamous cell carcinoma (OSCC) has shown a gradual increase in male predominance since the 1970s, despite reductions in smoking, as a result of the increasing incidence of HPV-associated OSCC. "
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    ABSTRACT: Oropharyngeal squamous cell carcinoma (OSCC) has shown a gradual increase in male predominance due to the increasing incidence of human papillomavirus (HPV)-associated OSCC. However, the mode of HPV transmission to the oral cavity is poorly understood, and little is known about the epidemiology of oral HPV infection in men. The prevalence rates of HPV, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma spp., and Ureaplasma spp. were compared in the oropharynx (oral cavity) and urine of male Japanese patients attending a sexually transmitted disease clinic. The study population consisted of 213 men aged 16 - 70 years old (mean: 34.4 years old). Oropharyngeal gargles and urine were collected, and sedimented cells were preserved in liquid-based cytology solution. After DNA extraction, beta-globin and infectious organisms were analyzed by a PCR-based method. The HPV genotype was determined by HPV GenoArray test. beta-Globin was positive in 100% and 97.7% of oral and urine samples, respectively. HPV detection rates were 18.8% and 22.1% in oral and urine samples, respectively, suggesting that the prevalence of HPV infection in the oral cavity was similar to that in the urinary tract. N. gonorrhoeae was more prevalent in oral (15.6%) than urine samples (9.1%), whereas C. trachomatis was detected more frequently in urine (15.9%) than oral samples (4.2%). The detection rates of M. genitalium, M. hominis, and Ureaplasma spp. were 5.2%, 10.3%, and 16.0% in oral samples, and 7.7%, 6.3%, and 19.2% in urine, respectively. There were no significant differences in the detection rates of Mycoplasma spp. and Ureaplasma spp. between anatomical locations. The distribution of HPV types were similar in oral and urine samples, and HPV16 was the most common type. The majority of men with HPV infection in both the oral cavity and urine had concordant oral and urinary HPV infection. The presence of urinary HPV infection was an independent risk factor of oral HPV infection, with an odds ratio of 3.39 (95%CI: 1.49 - 7.71), whereas oral gonococcal infection was inversely correlated with oral HPV infection (odds ratio: 0.096; 95%CI: 0.01 - 0.77). Oral HPV infection commonly occurs in sexually active men, and is significantly correlated with urinary HPV infection.
    Full-text · Article · Jan 2014 · BMC Infectious Diseases
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    • "Cervical cancer is the most common cause of mortality related to human papillomavirus [1] but HPV infection also raises important concerns for men. In fact, HPV has been associated with most male anal cancers (approximately 90%) and a subset of penile (50%) and oral cancers (10–72%) [2]. Additionally, the presence of HPV has been widely reported in semen [3], where it has been associated with impairment of sperm motility [4], supporting the hypothesis that HPV infection is an emerging risk factor for male infertility. "
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    ABSTRACT: Human papillomavirus (HPV) currently represents an important risk factor for cancer development and infertility in humans. Whilst binding of HPV to spermatozoa has been associated with male infertility, an investigation about the presence of HPV-DNA in non-spermatozoal semen cells is lacking. Previous findings documented the presence of HPV in peripheral blood leukocytes. The aim of this study was to investigate the expression of HPV markers in semen and blood leukocytes during HPV-16 infection. A total of 32 subjects, 16 patients affected by HPV-16 semen infection and 16 controls, were evaluated in our andrological centre and enrolled in the study. Semen non-spermatozoal cells from all subjects were isolated and evaluated for the expression of HPV-16 markers (DNA and L1, E6 proteins) and further characterized for their molecular phenotype. Analogue determination was performed on peripheral blood mononuclear cells. The presence of HPV-DNA by FISH analysis in a round cell population from semen, confirmed to be CD45+ leukocytes, was observed. These HPV-DNA containing-cells also displayed HPV-16-E6 and HPV-16-L1 viral proteins and, upon further investigation, were found to be CD20+ and CD56+, likely phenotypes of B cells and natural killer cells (NK) respectively. In 25% of the patient group, a very small population of peripheral blood mononuclear cells was found to be positive for HPV-DNA via FISH. These cells displayed the CD20+ and CD56+ phenotype alike. None of the control subjects displayed HPV-DNA in either semen or peripheral blood. Considering the role of CD20+ and CD56+ cell populations in the antiviral immune response, the detection of HPV markers on leukocytes may reflect the presence of virus particles within the endosomal compartment. However, the presence of HPV markers in circulating mononuclear cells raise concerns about the risk of developing cancers to distal organs.
    Full-text · Article · Dec 2013 · BMC Infectious Diseases
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