A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women
Elmar A Joura, Anna R Giuliano, Ole-Erik Iversen, Celine Bouchard, Constance Mao, Jesper Mehlsen, Edson D Moreira Jr, Yuen Ngan, Lone Kjeld Petersen, Eduardo Lazcano-Ponce, Punnee Pitisuttithum, Jaime Alberto Restrepo, Gavin Stuart, Linn Woelber, Yuh Cheng Yang, Jack Cuzick, Suzanne M Garland, Warner Huh, Susanne K Kjaer, Oliver M Bautista, Ivan S F Chan, Joshua Chen, Richard Gesser, Erin Moeller, Michael Ritter, Scott Vuocolo, Alain Luxembourg, Broad Spectrum HPV Vaccine Study, I Chan, J Chen, J Cuzick, R Gesser, A Luxembourg, R Gesser, A Giuliano, O E Iversen, E Joura, S K Kjaer, E Lazcano, C Mao, J Mehlsen, E Moeller, E Moreira, Y Ngan, L Petersen, P Pitisuttithum, J Restrepo, M Ritter, G Stuart, L Woelber, Y C Yang, O Bautista, I Chan, J Chen, O Bautista, I Chan, J Cuzick, S Garland, A Giuliano, W Huh, O E Iversen, E Joura, S K Kjaer, E Lazcano, A Luxembourg, C Mao, E Moreira, Y Ngan, L Petersen, M Ritter, S Vuocolo, E Joura, A Luxembourg, S Vuocolo, Olaf Reich, Rosires Andrade, Edison Fedrizzi, Murdo Ferguson, Robert Lotocki, Marie Helene Mayrand, Shelly McNeil, Deborah Money, Barbara Romanowski, Andree Vachon, Eugenio Suarez, Nestor Balcazar, Claudia Cecilia Cruz, Ana Maria Guevara, Joaquin Luna, Ivette Maldonado, Claudia Nossa, Manuel Plata, Francisco Revollo, Angela Maria Ruiz, Lina Trujillo, Alejandro Victoria, Erik Sogaard Andersen, Ole Mogensen, Klaus Greven, Kerstin Rhiem, Tak-Hong Cheung, Hideki Hanashi, Masaru Sakamoto, Nobuhiro Takeshima, Yuzuru Takeuchi, Wataru Tsunezawa, Chi-Heum Cho, Byoung Gie Kim, Seung Cheol Kim, Young Tak Kim, Hee-Sug Ryu, Yong Sang Song, Margarita Santiago, Susan Bagshaw, Stewart Reid, Helen Roberts, Knut Hesla, Grete Riis-Johannessen, Harald Moi, Terje Sordal, Kari Anne Trosterud, Robinson Cabello, Arnaldo Silva, Josefina Romaguera, Angelica Linden-Hirschberg, Sven Eric Olsson, Chi-An Chen, Hung-Hsueh Chou, Tang-Yuan Chu, Chung-Yuan Lee, Nae-Fang Twu, Mu-Hsien Yu, Nipon Khemapech, Sompong Koonlerkit, Sutham Pinjaroen, Sarikapan Wilailak, Mark Akin, Eugene Andruczyk, Kevin Ault, Stanley Block, Kirk Brody, Ramon Cestero, Daron Ferris, Stanley Gall, James Kratzer, Michelle Lally, Regina Lewis, Andrea Lukes, Scott Nicholson-Uhl, Lori Panther, Ronald Poblete, David Soper, Helen Lee Stacey, Michael Scutella, Marcia Shew, Jack Stapleton, Meera Varman, Dorothy Wiley, Molly Louise Yardley, Peter Zedler, Patricia Almeida Silva, Francine Do Amaral Barreto, Grete Hamre Augestad, Duk Soo Bae, Juan Bojanini, Andres Callamand, Rosangela Carniero, Chih Long Chang, Suk-Joon Chan, Pao-Chu Chen, Chang-Chang Cheng, Wen-Fang Chen, Jaime Andres Daste, Briyana Domjahn, Carolina de Andrade, Dah-Ching Ding, Kathy Eyring-Cabrera, Karina de Sá Adami Goncalves Brandaõ, Virginia Gonzalez, Friederike Greven, Kyung Hee Han, Rosalyn Hawkins, Chen Lai Hung, Joaquin Idrobo, Naoko Iwata, Jette Johansen, Woong Ju, Shara Karlebach, Susan Keast, Kayoko Kennedy, Hun Hwan Kim, Malene Kjærgaard Larsen, Tae-Wook Kong, Tabassam Latif, Shin Wha Lee, Elisabeth Leikvoll Enge, Kristiel Paola Leon Jimenez, Arb-Aroon Lertkhachonsuk, Hu Hsiang Lin, Paula Matos Oliveira, Erika Molina, Emilia Moreira Jalil, Jocelyn Morris, Fran Mulhall, Lyza Murillo, Martha Navarro, Hatsumi Norikyo, Kari Norstebo, Juliana Nossa Dominguez, Suaree Ontrakan, Betty Oswald, Sophie Pils, Katharina Prieske, Ivana Rastigorac, James Reid, Ricardo Rincon Molano, Sandra Patricia Rodriguez Garcia, Manuel Salhuana, Eduardo Salvatierra, So Jin Shin, Karine Souza Da Corregghio, Jatripol Srisomboon, Mayumi Taniguchi, Chih Jen Tseng, Hsin-Shih Wang, Kung-Liang Wang, Chiaki Yoshioka, Melissa Catlett, Karen Conway, Roger Maansson, Deborah Marino, Christine Roberts, Christine Shields, Xiao Sun, Brynne Tannenbaum, Jack Cuzick, Suzanne Garland, Anna Giuliano, Elizabeth Halloran, Warner Huh, Ole-Erik Iversen, Elmar Joura, Susanne Kruger-Kjaer, Dianne Miller, Alex Ferenczy, Robert Kurman, Brigitte M Ronnett, Mark H Stoler, Philip Castle, Tom Cox, Froydis Langmark, John Modlin, Alvaro Munoz, Bruce Patterson, Edward Wilkinson, Elmar A Joura, Anna R Giuliano, Ole-Erik Iversen, Celine Bouchard, Constance Mao, Jesper Mehlsen, Edson D Moreira Jr, Yuen Ngan, Lone Kjeld Petersen, Eduardo Lazcano-Ponce, Punnee Pitisuttithum, Jaime Alberto Restrepo, Gavin Stuart, Linn Woelber, Yuh Cheng Yang, Jack Cuzick, Suzanne M Garland, Warner Huh, Susanne K Kjaer, Oliver M Bautista, Ivan S F Chan, Joshua Chen, Richard Gesser, Erin Moeller, Michael Ritter, Scott Vuocolo, Alain Luxembourg, Broad Spectrum HPV Vaccine Study, I Chan, J Chen, J Cuzick, R Gesser, A Luxembourg, R Gesser, A Giuliano, O E Iversen, E Joura, S K Kjaer, E Lazcano, C Mao, J Mehlsen, E Moeller, E Moreira, Y Ngan, L Petersen, P Pitisuttithum, J Restrepo, M Ritter, G Stuart, L Woelber, Y C Yang, O Bautista, I Chan, J Chen, O Bautista, I Chan, J Cuzick, S Garland, A Giuliano, W Huh, O E Iversen, E Joura, S K Kjaer, E Lazcano, A Luxembourg, C Mao, E Moreira, Y Ngan, L Petersen, M Ritter, S Vuocolo, E Joura, A Luxembourg, S Vuocolo, Olaf Reich, Rosires Andrade, Edison Fedrizzi, Murdo Ferguson, Robert Lotocki, Marie Helene Mayrand, Shelly McNeil, Deborah Money, Barbara Romanowski, Andree Vachon, Eugenio Suarez, Nestor Balcazar, Claudia Cecilia Cruz, Ana Maria Guevara, Joaquin Luna, Ivette Maldonado, Claudia Nossa, Manuel Plata, Francisco Revollo, Angela Maria Ruiz, Lina Trujillo, Alejandro Victoria, Erik Sogaard Andersen, Ole Mogensen, Klaus Greven, Kerstin Rhiem, Tak-Hong Cheung, Hideki Hanashi, Masaru Sakamoto, Nobuhiro Takeshima, Yuzuru Takeuchi, Wataru Tsunezawa, Chi-Heum Cho, Byoung Gie Kim, Seung Cheol Kim, Young Tak Kim, Hee-Sug Ryu, Yong Sang Song, Margarita Santiago, Susan Bagshaw, Stewart Reid, Helen Roberts, Knut Hesla, Grete Riis-Johannessen, Harald Moi, Terje Sordal, Kari Anne Trosterud, Robinson Cabello, Arnaldo Silva, Josefina Romaguera, Angelica Linden-Hirschberg, Sven Eric Olsson, Chi-An Chen, Hung-Hsueh Chou, Tang-Yuan Chu, Chung-Yuan Lee, Nae-Fang Twu, Mu-Hsien Yu, Nipon Khemapech, Sompong Koonlerkit, Sutham Pinjaroen, Sarikapan Wilailak, Mark Akin, Eugene Andruczyk, Kevin Ault, Stanley Block, Kirk Brody, Ramon Cestero, Daron Ferris, Stanley Gall, James Kratzer, Michelle Lally, Regina Lewis, Andrea Lukes, Scott Nicholson-Uhl, Lori Panther, Ronald Poblete, David Soper, Helen Lee Stacey, Michael Scutella, Marcia Shew, Jack Stapleton, Meera Varman, Dorothy Wiley, Molly Louise Yardley, Peter Zedler, Patricia Almeida Silva, Francine Do Amaral Barreto, Grete Hamre Augestad, Duk Soo Bae, Juan Bojanini, Andres Callamand, Rosangela Carniero, Chih Long Chang, Suk-Joon Chan, Pao-Chu Chen, Chang-Chang Cheng, Wen-Fang Chen, Jaime Andres Daste, Briyana Domjahn, Carolina de Andrade, Dah-Ching Ding, Kathy Eyring-Cabrera, Karina de Sá Adami Goncalves Brandaõ, Virginia Gonzalez, Friederike Greven, Kyung Hee Han, Rosalyn Hawkins, Chen Lai Hung, Joaquin Idrobo, Naoko Iwata, Jette Johansen, Woong Ju, Shara Karlebach, Susan Keast, Kayoko Kennedy, Hun Hwan Kim, Malene Kjærgaard Larsen, Tae-Wook Kong, Tabassam Latif, Shin Wha Lee, Elisabeth Leikvoll Enge, Kristiel Paola Leon Jimenez, Arb-Aroon Lertkhachonsuk, Hu Hsiang Lin, Paula Matos Oliveira, Erika Molina, Emilia Moreira Jalil, Jocelyn Morris, Fran Mulhall, Lyza Murillo, Martha Navarro, Hatsumi Norikyo, Kari Norstebo, Juliana Nossa Dominguez, Suaree Ontrakan, Betty Oswald, Sophie Pils, Katharina Prieske, Ivana Rastigorac, James Reid, Ricardo Rincon Molano, Sandra Patricia Rodriguez Garcia, Manuel Salhuana, Eduardo Salvatierra, So Jin Shin, Karine Souza Da Corregghio, Jatripol Srisomboon, Mayumi Taniguchi, Chih Jen Tseng, Hsin-Shih Wang, Kung-Liang Wang, Chiaki Yoshioka, Melissa Catlett, Karen Conway, Roger Maansson, Deborah Marino, Christine Roberts, Christine Shields, Xiao Sun, Brynne Tannenbaum, Jack Cuzick, Suzanne Garland, Anna Giuliano, Elizabeth Halloran, Warner Huh, Ole-Erik Iversen, Elmar Joura, Susanne Kruger-Kjaer, Dianne Miller, Alex Ferenczy, Robert Kurman, Brigitte M Ronnett, Mark H Stoler, Philip Castle, Tom Cox, Froydis Langmark, John Modlin, Alvaro Munoz, Bruce Patterson, Edward Wilkinson
Abstract
Background: The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age.
Methods: We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV.
Results: The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group.
Conclusions: The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).
Source: PubMed