Laia Alemany1, Antonio Cubilla2, Gordana Halec3, Elena Kasamatsu2, Beatriz Quirós4, Emili Masferrer5, Sara Tous4, Belén Lloveras5, Gustavo Hernández-Suarez6, Ray Lonsdale7, Leopoldo Tinoco8, Maria Alejo9, Isabel Alvarado-Cabrero10, Jan Laco11, Nuria Guimerà12, Enrique Poblet13, Luis E Lombardi14, Christine Bergeron15, Omar Clavero4, Hai-Rim Shin16, Annabelle Ferrera17, Ana Felix18, Julieta Germar19, Vaclav Mandys20, Christine Clavel21, Maria Tzardi22, Luis E Pons23, Vincent Wain24, Eugenia Cruz25, Carla Molina26, Jose D Mota27, Robert Jach28, Julio Velasco29, Carla Carrilho30, Ruben López-Revilla31, Marc T Goodman32, Wim G Quint12, Xavier Castellsagué4, Ignacio Bravo4, Michael Pawlita3, Nubia Muñoz33, F Xavier Bosch4, Silvia de Sanjosé34. 1. Institut Català d'Oncologia, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. Electronic address: lalemany@iconcologia.net. 2. Instituto de Investigaciones en Ciencias de la Salud-Universidad Nacional de Asunción, Asunción, Paraguay. 3. German Cancer Research Center (DKFZ), Heidelberg, Germany. 4. Institut Català d'Oncologia, Barcelona, Spain. 5. Hospital del Mar, Barcelona, Spain. 6. Instituto Nacional de Cancerología, Bogotá, Colombia. 7. Norfolk and Norwich University Hospital NHS Foundation Trust, Norfolk, UK. 8. Hospital Oncológico, Quito, Ecuador. 9. Hospital General Hospitalet, Barcelona, Spain. 10. Hospital de Oncología Centro Médico Nacional Siglo XXI, IMSS Mexico, D.F, Mexico. 11. The Fingerland Department of Pathology, Charles University in Prague Faculty of Medicine and University Hospital, Hradec Králové, Czech Republic. 12. DDL Diagnostic Laboratory, Rijswijk, The Netherlands. 13. Hospital General Universitario de Albacete, Albacete, Spain. 14. Centro de Investigación Epidemiológica en Salud Sexual y Reproductiva-CIESAR, Hospital General San Juan de Dios, Guatemala City, Guatemala. 15. Laboratoire Cerba, Saint-Ouen-l'Aumône, France. 16. National Cancer Center, Goyang-si Gyeonggi-do, South Korea. 17. Universidad Autónoma de Honduras, Tegucigalpa, Honduras. 18. Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal. 19. University of Philippines, Manila, Philippines. 20. Third Faculty of Medicine, Charles University and Faculty Hospital King's Vineyards, Prague, Czech Republic. 21. CHU Reims, Reims, France. 22. Medical School of University of Crete, Crete, Greece. 23. Hospital de Tortosa Verge de la Cinta, Tarragona, Spain. 24. Westmead Hospital, Westmead, Australia. 25. Centro de Oncología de Coimbra, Coimbra, Portugal. 26. Universidad de Chile, Santiago, Chile. 27. Universidad Central de Venezuela, Caracas, Venezuela. 28. Jagiellonian University Medical College, Krakow, Poland. 29. Hospital San Agustín, Asturias, Spain. 30. Eduardo Mondlane University and Maputo Central Hospital, Maputo, Mozambique. 31. Instituto Potosino de Investigación Científica y Tecnológica, San Luis Potosí, Mexico. 32. Cancer Research Center, University of Hawaii, Honolulu, HI, USA; Cedars Sinai Medical Center, Los Angeles, CA, USA. 33. National Cancer Institute of Colombia, Bogota, Colombia. 34. Institut Català d'Oncologia, Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
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 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. 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 p16(INK4a) 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 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. 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.
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 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. 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 p16(INK4a) 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 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. 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.
Authors: Stefanie J Klug; Marianne van der Sande; Martin Terhardt; Fred Zepp; Marianne Röbl-Mathieu; Jörg Meerpohl; Miriam Wiese-Posselt; Thomas Harder; Ole Wichmann; Anja Takla Journal: Urologe A Date: 2018-11 Impact factor: 0.639