Role of Human Papillomavirus in Penile Carcinomas Worldwide

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.

To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16(INK4a)) 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.

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 p16(INK4a) expression, a surrogate marker of oncogenic HPV activity.

HPV DNA prevalence and type distributions were estimated.

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 p16(INK4a) 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.

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.

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.

European urology. 2016 Jan 04 [Epub ahead of print]

Laia Alemany, Antonio Cubilla, Gordana Halec, Elena Kasamatsu, Beatriz Quirós, Emili Masferrer, Sara Tous, Belén Lloveras, Gustavo Hernández-Suarez, Ray Lonsdale, Leopoldo Tinoco, Maria Alejo, Isabel Alvarado-Cabrero, Jan Laco, Nuria Guimerà, Enrique Poblet, Luis E Lombardi, Christine Bergeron, Omar Clavero, Hai-Rim Shin, Annabelle Ferrera, Ana Felix, Julieta Germar, Vaclav Mandys, Christine Clavel, Maria Tzardi, Luis E Pons, Vincent Wain, Eugenia Cruz, Carla Molina, Jose D Mota, Robert Jach, Julio Velasco, Carla Carrilho, Ruben López-Revilla, Marc T Goodman, Wim G Quint, Xavier Castellsagué, Ignacio Bravo, Michael Pawlita, Nubia Muñoz, F Xavier Bosch, Silvia de Sanjosé, HPV VVAP study group

Institut Català d'Oncologia, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. Instituto de Investigaciones en Ciencias de la Salud-Universidad Nacional de Asunción, Asunción, Paraguay. , German Cancer Research Center (DKFZ), Heidelberg, Germany. , Instituto de Investigaciones en Ciencias de la Salud-Universidad Nacional de Asunción, Asunción, Paraguay. , Institut Català d'Oncologia, Barcelona, Spain. , Hospital del Mar, Barcelona, Spain. , Institut Català d'Oncologia, Barcelona, Spain. , Hospital del Mar, Barcelona, Spain. , Instituto Nacional de Cancerología, Bogotá, Colombia. , Norfolk and Norwich University Hospital NHS Foundation Trust, Norfolk, UK. , Hospital Oncológico, Quito, Ecuador. , Hospital General Hospitalet, Barcelona, Spain. , Hospital de Oncología Centro Médico Nacional Siglo XXI, IMSS Mexico, D. F, Mexico. , The Fingerland Department of Pathology, Charles University in Prague Faculty of Medicine and University Hospital, Hradec Králové, Czech Republic. , DDL Diagnostic Laboratory, Rijswijk, The Netherlands. , Hospital General Universitario de Albacete, Albacete, Spain. , Centro de Investigación Epidemiológica en Salud Sexual y Reproductiva-CIESAR, Hospital General San Juan de Dios, Guatemala City, Guatemala. , Laboratoire Cerba, Saint-Ouen-l'Aumône, France. , Institut Català d'Oncologia, Barcelona, Spain. , National Cancer Center, Goyang-si Gyeonggi-do, South Korea. , Universidad Autónoma de Honduras, Tegucigalpa, Honduras. , Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal. , University of Philippines, Manila, Philippines. , Third Faculty of Medicine, Charles University and Faculty Hospital King's Vineyards, Prague, Czech Republic. , CHU Reims, Reims, France. , Medical School of University of Crete, Crete, Greece. , Hospital de Tortosa Verge de la Cinta, Tarragona, Spain. , Westmead Hospital, Westmead, Australia. , Centro de Oncología de Coimbra, Coimbra, Portugal. , Universidad de Chile, Santiago, Chile. , Universidad Central de Venezuela, Caracas, Venezuela. , Jagiellonian University Medical College, Krakow, Poland. , Hospital San Agustín, Asturias, Spain. , Eduardo Mondlane University and Maputo Central Hospital, Maputo, Mozambique. , Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, Mexico. , Cancer Research Center, University of Hawaii, Honolulu, HI, USA; Cedars Sinai Medical Center, Los Angeles, CA, USA. , DDL Diagnostic Laboratory, Rijswijk, The Netherlands. , Institut Català d'Oncologia, Barcelona, Spain. , Institut Català d'Oncologia, Barcelona, Spain. , German Cancer Research Center (DKFZ), Heidelberg, Germany. , National Cancer Institute of Colombia, Bogota, Colombia. , Institut Català d'Oncologia, Barcelona, Spain. , Institut Català d'Oncologia, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.

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