Guimera, N. et al., LR-HPVs in Anogenital Carcinomas Supplemental digital content Supplemental digital content 1, Table, Number of invasive cervical, vagina, vulva, penile and anal cancers by patient age, histological categories, HPV genotypes on whole tissue sections and tumour cells by LCM and p16INK4A staining Localization Country Age Diagnosis: H&E-1, H&E-2 and H&E-3* Intake HPV genotype HPV genotype/s on whole tissue sections from PCR-1 / PCR-2 p16 INK4A staining LCM HPV genotype in tumor cells HPV genotype in non-tumor cells† % of tumor cells stained Pattern Grade Cervix (n=21) Korea, S 40 Papillary squamous transitional cell carcinoma 6 6 / NA 6 NA NA NA Spain 45 Papillary squamous transitional cell carcinoma 6 6/6 6 0 0 0 Colombia 40 Papillary squamous transitional cell carcinoma 6 6/6 6 26-50 Patchy 2 Spain Unknown Papillary squamous transitional cell carcinoma 6 6/6 6 1-25 Patchy 1 France 31 Papillary squamous transitional cell carcinoma 6 6/6 6 0 0 0 Venezuela 50 Papillary squamous transitional cell carcinoma 6 6/6 6 26-50 Patchy 2 Colombia 77 Classical adenocarcinoma 6 6/6 -‡ 0 0 0 Korea, S 36 Papillary squamous transitional cell carcinoma 11 11 / NA 11 NA NA NA BosniaHerzegovina 72 Squamous cell carcinoma 42 42 / 42 42 26-50 Patchy 2 Unknown Squamous cell carcinoma 42 42 / 42 42 >50 Diffuse 3 Italy 78 Squamous cell carcinoma 42 42 / NA 42 NA NA NA BosniaHerzegovina 57 Squamous cell carcinoma 44 44 / -§ -§ 0 0 0 Brazil 56 Squamous cell carcinoma 70 70 / NA 70 NA NA NA Philippines 66 Squamous cell carcinoma 70 70 / 70 70 >50 Diffuse 3 Colombia 48 Squamous cell carcinoma 70 70 / 70 70 >50 Diffuse 3 Lebanon Unknown Squamous cell carcinoma 70 70 / 70 70 >50 Diffuse 3 Lebanon 54 Squamous cell carcinoma 70 70 / 70 70 >50 Diffuse 3 Mexico 50 Squamous cell carcinoma 70 70 / -§ -‡ >50 Diffuse 3 Italy 75 Squamous cell carcinoma 70 70 / NA 70 NA NA NA Thailand 44 Squamous cell carcinoma 70 70 / NA -§ NA NA NA Taiwan 41 Adenosquamous carcinoma 70 70 / -§ 70 >50 Diffuse 3 Portugal 6 -§ ║ -§ Vagina Page 1 of 5 Guimera, N. et al., LR-HPVs in Anogenital Carcinomas (n=1) Mexico 82 Papillary squamous transitional cell carcinoma 6 6¶ / 6 6 0 0 0 Guatemala 78 Squamous cell carcinoma 6 6/6 6 Colombia 79 Squamous cell carcinoma 6 -§/6 -§ -§ 0 0 0 26-50 Patchy 2 Portugal 72 Squamous cell carcinoma 44 44 / 44 -‡ 44 0 0 0 Austria 79 Squamous cell carcinoma 44 44 / 44 -§ -§ 0 0 0 Austria 79 Warty-Basaloid carcinoma 44 44 / 44 44 0 0 0 Chile 45 Verrucous carcinoma 6 6/6 6 0 0 0 France 48 Verrucous carcinoma 6 6/6 6 1-26 Patchy 1 France 51 Verrucous carcinoma 6 6/6 6 Portugal 70 Basaloid carcinoma 42 42 / 42 42 0 0 0 >50 Diffuse 3 Paraguay 45 Squamous cell carcinoma 6 6 / -§ -‡ 0 0 0 Paraguay 53 Warty carcinoma 6 6/6 6 1-26 Patchy 1 Paraguay 74 Warty carcinoma 6 Paraguay Unknown Warty carcinoma 6 6/6 6 1-26 Patchy 1 6/6 6 0 0 0 Paraguay 52 Warty carcinoma 6 6/6 6 1-26 Patchy 1 Paraguay 75 Papillary squamous carcinoma 6 6/6 -§ 0 0 0 Guatemala Colombia 40 Warty-Basaloid carcinoma 6 6/6 6 0 0 0 45 Warty carcinoma 6 6/6 6 1-26 Patchy 1 Czech republic 75 Squamous cell carcinoma 6 -§/-§ Excluded N.D N.D N.D Guatemala 47 Squamous cell carcinoma 11 11 / 11 -‡ -‡ 0 0 0 Guatemala 47 Papillary squamous carcinoma 11 11 / 11 -§ -‡ 0 0 0 Guatemala 66 Squamous cell carcinoma 11 11 / 11 11 0 0 0 Paraguay 65 Squamous cell carcinoma 11 -§ / -§ Excluded N.D N.D N.D Paraguay 73 Warty-Verrucous carcinoma 40 6, 40 Excluded N.D N.D N.D Squamous cell carcinoma 70 70 / -§ 70 >50 Diffuse 3 Vulva (n=5) Anus (n=4) Penis (n=15) Mexico Unknown † -‡ -‡ ‡ *H&E-3 was only analyzed on cases with block available; In cases where HPV was negative in tumor cells by LCM, other regions were analyzed like: normal epithelium, debris or pre-neoplasic lesions; Human endogenous control gene negative; § Human endogenous control gene positive; ║Only tumor cells present ; ¶Only sequencing confirmation on 104bp from L1 ORF; NA, No material available for testing; -, Negative; N.D, Not Done. Page 2 of 5 Guimera, N. et al., LR-HPVs in Anogenital Carcinomas RIS HPV TT/HPV VVAPO study group: 1. Algeria: Doudja Hammouda (National Institute of Health, Registre des Tumeurs d’Alger), Anissa Bouhadef (C.H.U Hussein-Dey- Hospital Nafissa Hamoud). 2. Argentina: Silvio Alejandro Tatti, Susana Vighi (Hospital de Clínicas José de San Martín, Universidad de Buenos Aires), Myriam Beatriz Perrota, Ana Jaen, Davis Kevin (Hospital Italiano de Buenos Aires) 3. Australia: Suzanne M. Garland, Sepher Tabrizi (The Royal Women’s Hospital, The University of Melbourne), Gerard Vincent Wain, Catherine J Kennedy, Raghwa Sharma, Yoke-Eng Chiew (Gynaecological Oncology, Westmead Hospital) 4. Austria: Elmar Armin Joura (University Hospital and Medical School) 5. Bangladesh: Ashrafun Nessa, AJE Nahar Rahman, Mohammad Kamal (Bangabandhu Sheikh Mujib Medical University – BSMMU), Faruk Ahmed (Dhaka Medical College Hospital) 6. Belarus: Halina Viarheichyk, Sitnikov Valeriy (Gomel State Medical University), Achynovich Searhei (Gomel Regional Clinical Oncological Hospital) 7. Bosnia Herzegovina: Ermina Iljazovic (University Clinical Center Tuzla BiH). 8. Brazil: Marcus Aurelho de Lima, Sérgio Henrique (Laboratório de Anatomia Patológica e Citologia Ltda, Associação de Combate ao Câncer do Brasil Central, Hospital Dr. Hélio Angotti, PATMED), Paula Maldonado, Marcia Mannarino, Yara Furtado, Roberto Jose Lima, Gutemberg Leão Almeida, Isabel Val, Renata Fonseca (Instituto de Ginecologia da Universidad Federal do Rio de Janeiro). 9. Chile: Rodrigo Prado (Centro de Oncología Preventiva, Facultad de Medicina, Universidad de Chile), Ximena Rodriguez, Marisol Guerrero,Virginia Leiva, Elsa Olave, Claudia Ramis, Viviana Toro (Complejo Hospitalario San José). 10. China: You Lin Qiao, Chen Wen, Wu Su Hui (Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College). 11. Colombia: Hector Jaime Posso (Liga Contra el Cáncer de Bogotá), Luis Eduardo Bravo, Tito Collazos, Luz Stella García (Hospital Universitario del Valle), Raúl Murillo, Gustavo Adolfo Hernández Suárez, Carlos Eduardo Pinzón (Instituto Nacional de Cancerología), Gloria I. Sánchez (Universidad de Antioquía). 12. Croatia: Magdalena Grce, Ivan Sabol (Rudjer Boskovic Institutem), Sonja Dzebro, Mara Dominis (Clinical Hospital Merkur). 13. Czech Republic: Ivo Steiner (Faculty of Medicine and Faculty Hospital, Hradec Kralove), Vladimir Vonka (Institute of Hematology and Blood Transfusion), Václav Mandys (3rd Faculty of Medicine and University Hospital King’s Wineyards) 14. Ecuador: Leopoldo Tinoco (Hospital Oncológico de Quito) 15. France: Christine Clavel, Philippe Birembaut, Veronique Dalstein (CHU Reims, Laboratoire Pol Bouin, Hôpital Maison Blanche), Massimo Tommasino (International Agency for Research on Cancer), Christine Bergeron (Laboratoire Pasteur-Cerba, Departement de Pathologie) 16. Germany: Monika Hampl, Pof. Baldus (University Hospital of Duesseldorf), Karl Ulrich Petry, Alexander Luyten (Klinikum Wolfsburg) Page 3 of 5 Guimera, N. et al., LR-HPVs in Anogenital Carcinomas 17. Greece: Maria Tzardi (Medical School of University of Crete), Theodoros Agorastos (Aristotle University of Thessaloniki). 18. Guatemala: Luis Estuardo Lombardi, Edgar Kestler, Obdulia Salic, Sergio Marroquin, Victor Argueta, Walter Guerra, Sergio Marroquin (Centro de Investigación Epidemiológica en Salud Sexual y Reproductiva - CIESAR, Hospital General San Juan de Dios), Walter Guerra, Hesler Morales (Instituto Nacional del Cáncer). 19. Honduras: Annabelle Ferrera (Escuela de Microbiología, Universidad Nacional Autónoma de Honduras), Ricardo Bulnes (Hospital General San Felipe). 20. India: Asha Jain (Cancer Prevention and Relief Society Raipur), PSA Sarma (BSP Hospital), Sushil K Giri (Regional Cancer Center); Maheep Bhalla (JLN Hospital & Research Center), Bharat Patel (Lab One), Neerja Bhatla, Manju Aron, Sandeep Mathur (Institute of Medical Science New Dehli), Ravi Mehrotra (M.L.N Medical College , Raipur), 21. Italy: Luciano Mariani, Ferdinando Marandino, Amina Vocaturo, Maria Benevolo (Regina Elena Cancer Institute). 22. Israel: Jacob Bornstein, Alejandro Livoff, Hector Itzhac Cohen (Western Galilee Hospital). 23. Japan: Toshiyuki Sasagawa (Kanazawa University Hospital), Shintaro Terahata (Tonami General Hospital), Kazuhisa Ishi (Juntendo University, Urayasu Hospital). 24. South Korea: Hai-Rim Shin, Jin-Kyoung Oh (National Cancer Center), Jung-II Suh (National Medical Center), Seo-Hee Rha (Dong-A University), Shin Gwang Kang (Asan Medical Center), Dong-chul Kim (Kangnam St. Mary's Hospital) 25. Kuwait: Waleed Fahad Al-Jassar (Faculty of Medicine, Kuwait University), Rema’a Al-Safi (Maternity Hospital). 26. Lebanon: Muhieddine Seoud (The American University of Beirut Medical Center). 27. México: Patricia Alonso de Ruiz, Gustavo Lastra, Alma Karina Olivares Montano (Hospital General de México, Facultad de Medicina, Universidad Nacional Autónoma de México), Jorge Salmeron, Isabel Alvarado-Cabrero (Instituto Mexicano del Seguro Social), Rubén López-Revilla, Cuauhtémoc Oros Ovalle, Claudia Magaña (Instituto Potosino de Investigación Científica y Tecnológica, AC), Ignacio Morones Prieto (Hospital Central, San Luis Potosí). 28. Mozambique: Clara Menéndez, Cleofé Romagosa, Carla Carrillo (Barcelona Center for International Health Research, Hospital Clínic/Universitat de Barcelona, and Manhiça Health Research Center). 29. New Zealand: Susan M Bigby, RW Jones, KL Fong, D Rowan, J Baranyai, L Eva (Middlemore Hospital) 30. Nigeria: Adekunbiola Banjo, Rose Anorlu, Fatimah B. Abdulkareem, A.O Daramola, CC Anunobi (Lagos University Teaching Hospital Idi-Araba), Sani Malami, Ali Bala Umar (Faculty of Medicine, Bayero University) 31. Paraguay: Elena Kasamatsu, Francisco Perrota, Antonio Cubilla (Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción). 32. Perú: Carlos Santos, Eduardo Cáceres, Henry Gómez, Juvenal Sánchez, Carlos S. Vallejos, (Instituto Nacional de Enfermedades Neoplásicas). Page 4 of 5 Guimera, N. et al., LR-HPVs in Anogenital Carcinomas 33. The Philippines: Efren J. Domingo, María Julieta V. Germar, Jericho Thaddeus P. Luna, Maria Julieta V. Germar, Carolyn Zalameda-Castro, Arnold M. Fernandez, Roslyn Balacuit (University of the Philippines College of Medicine); Cecilia Ladines Llave, Jean Anne Toral (Cervical Cancer Prevention Center – CECAP, Cancer Institute (UPCM-PGH)). 34. Poland: Andrzej Marcin Nowakowski (Medical University of Lublin), Robert Jach, Jolanta Orlowska-Heitzman, Monika Kabzinska-Turek, Paulina Przybylska, Marzena kula-Prykan (Jagiellonian University Medical College) 35. Portugal: Eugenia Cruz (Centro Regional de Oncologia Coimbra, Instituto Português de Oncologia); Manuela Lacerda, Manuel Sobrinho-Simoes (Institute of Molecular Pathology and Immunology of the University of Porto); Ana Felix, Jorge Manuel Soares (Instituto Portugues de Oncologia de Lisboa Francisco Gentil). 36. Spain: Enrique Lerma (Hospital de la Santa Creu i Sant Pau); Enrique Poblet (Hospital General Universitário de Albacete); Lluís Eleuteri Pons, Patrícia Escrivà Beltri, Marylene Lejeune (Hospital de Tortosa Verge de La Cinta); Antonio Llombart-Bosch, Morelva Toro de Méndez (Facultad de Medicina, Universidad de Valencia); Belen Lloveras, Mar Iglesias, Emili Masferrer (Hospital del Mar); Ana Puras Gil (Hospital Virgen del Camino); Miguel Andújar (Complejo Hospitalario Universitario Insular Marteno-Infantil); Jaume Ordi, Llucia Alòs (CRESIB - Hospital Clínic); Adela Pelayo (Clinica San Carlos); Julio Velasco, Cristina Pérez (Hospital San Agustín, & IUOPA (Oncologic and Universitary Institute of Principality of Astúrias)); Maria Alejo (Hospital General de l’Hospitalet); Laia Alemany, F. Xavier Bosch, Vanesa Camón, Xavier Castellsagué, Omar Clavero, Silvia de Sanjosé, Mireia Diaz, Ana Esteban, Jose M. Godínez, Ignacio G. Bravo, Nuria Guimerà, Yolanda Florencia, Jô Ellen Klaustermeier, Nubia Muñoz, Bea Quirós Cristina Rajo, Sara Tous, Marleny Vergara, (IDIBELL, Institut Català d’Oncologia (ICO) - Catalan Institute of Oncology); August Vidal (Hospital Universitari de Bellvitge). 37. Taiwan: Chou Cheng-Yang (National Cheng Kung University Medical College, Taiwan Association of Gynecologic Oncologists); Tang-Yuan Chu (Buddhist Tzuchi Genral Hospital); Kuo-Feng Huang (Chi Mei Medical Center); Cheng Wen-Fang (National Taiwan University Hospital); Chih- Ming HO (Gynecologic Cancer Center, Cathay General Hospital). 38. Thailand: Saibua C. Bunnag Chichareon, Kobkul Tungsinmunkong, Jintamard Suwanjarat (Prince of Songkla University). 39. The Netherlands: Chris J.L.M Meijer, Peter J.F Snijders (Vrije Universiteit Medical Center); Wim G.V. Quint, Jean-Paul Brunsveld, Anco C. Molijn, Daan T. Geraets, Jan Lindeman, David Jenkins, Annet Westbroek, René Bax, Linda Struijk, Bernhard Kleter, Maurits de Koning (DDL Diagnostic Laboratory). 40. Turkey: Alp Usubutun (Medical School, Hacettepe University). 41. Uganda: Michael Odida (Uganda Makerere University); Elisabete Weiderpass (Karolinska Institutet, Sweden; The Norwegian Cancer Registry, Norway; Samfunded Folkhalsan, Finland). 42. UK: Robyn Davies (Manchester Royal Infirmary), Paul Cross (Queen Elizabeth Hospital, Sheriff Hill), Ray Lonsdale (Norfolk & Norwich University Hospital NHS Foundation Trust) 43. Uruguay: Adela Rosa Sica, Benedicta Caserta, Mabel Cedeira, Daniel Mazal, Guillermo Rodríguez (Laboratorio de Anatomía Patológica del Hospital de la Mujer, Montevideo) 44. United States of America: Esther Oliva (Massachusetts General Hospital); Thomas C. Wright (New York Presbyterian Hospital, Columbia University Medical Center), Edyta Pirog (New York Hospital - Cornell Medical Centre), Mark T Goodman, Brenda Y Hernandez (University of Hawaii, Cancer Center, Honolulu, Hawaii) 45. Venezuela: Enrique López Loyo (Sociedad Venezolana de Patología); Victoria García Barriola, Mirian Naranjo de Gómez, Adayza Figueredo, Janira Navarro (Universidad Central de Venezuela). Page 5 of 5