TY - JOUR
T1 - Human Papillomavirus Genotypes from Vaginal and Vulvar Intraepithelial Neoplasia in Females 15-26 Years of Age
AU - Garland, Suzanne M.
AU - Joura, Elmar A.
AU - Ault, Kevin A.
AU - Bosch, F. Xavier
AU - Brown, Darron R.
AU - Castellsagué, Xavier
AU - Ferenczy, Alex
AU - Ferris, Daron Gale
AU - Giuliano, Anna R.
AU - Hernandez-Avila, Mauricio
AU - Huh, Warner K.
AU - Iversen, Ole Erik
AU - Kjaer, Susanne K.
AU - Kurman, Robert J.
AU - Luna, Joaquin
AU - Monsonego, Joseph
AU - Muñoz, Nubia
AU - Paavonen, Jorma
AU - Pitisuttihum, Punnee
AU - Ronnett, Brigitte M.
AU - Steben, Marc
AU - Stoler, Mark H.
AU - Wheeler, Cosette M.
AU - Wiley, Dorothy J.
AU - Perez, Gonzalo
AU - Saah, Alfred J.
AU - Luxembourg, Alain
AU - Li, Se
AU - DiNubile, Mark J.
AU - Wagner, Monika
AU - Velicer, Christine
N1 - Funding Information:
All academic authors have been investigators for Merck & Co, Inc., Kenilworth, New Jersey. Dr. Garland reports having received funding through her institution to perform human papillomavirus (HPV) vaccine studies for Merck & Co, Inc., CSL Limited, and GlaxoSmithKline; received payment for board membership on the Merck Global Advisory Board; and received honoraria for lectures including services on a speakers’ bureau conducted during her personal time; she also serves as co-chair of the PATRICIA publication steering committee. Dr. Joura reports having received grant support paid to his institution from Merck & Co, Inc. and GlaxoSmithKline; advisory board fees from Merck & Co, Inc. and Sanofi Pasteur MSD, and lecture fees from Sanofi Pasteur MSD, Merck & Co, Inc., GlaxoSmithKline, and Roche. Dr. Ault has received grants to his institution from Merck & Co, Inc. and the National Institutes of Health and advisory committee fees from the American College of Obstetricians and Gynecologists. He also serves on the editorial board for the National Cancer Institute. Dr. Bosch has received institutional research and educational grants from Sanofi Pasteur MSD and GlaxoSmithKline and personal travel grant and speakers’ honorarium from Sanofi Pasteur MSD and GlaxoSmithKline. Dr. Brown has served on an advisory board at Merck & Co, Inc. and has lectured on the quadrivalent HPV vaccine (honoraria received from Merck & Co, Inc. are donated to charities). His laboratory has received research funding from Merck & Co, Inc. Indiana University and Merck &Co, Inc. have an agreement that pays the university based on certain landmarks related to vaccine development. Dr. Brown receives a portion of these funds as income. Dr. Castellsagué received institutional research and educational grants from Sanofi Pasteur MSD, Merck & Co, Inc., GlaxoSmithKline, and Genticel and occasional personal travel grants and speakers’ honoraria from Sanofi Pasteur MSD and Vianex. Dr. Castellsagué’s family has given permission that he may be listed as a coauthor in this article. Dr. Ferenczy is a member of the Pathology Panel for Merck & Co, Inc. randomized controlled vaccine trials. Dr. Ferris has received grants to his institution and lecture fees from Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc., and advisory board and consultant fees from Merck & Co, Inc. Dr. Giuliano has received grant support and advisory board member fees to her institution from Merck & Co, Inc. Dr. Huh has received honoraria for advisory board participation with Merck & Co, Inc. Dr. Iversen has received compensation from Merck & Co, Inc. and GlaxoSmithKline to conduct vaccine clinical trials as well as scientific advisory board fees from Merck & Co, Inc. Dr. Kjaer has received scientific advisory board and speakers’ fees from Sanofi Pasteur MSD and Merck & Co, Inc. and unrestricted research grants through her institution from Merck & Co, Inc. and scientific advisory board fees from Becton Dickinson. Dr. Kurman is a member of the Pathology Panel for Merck & Co, Inc. randomized controlled vaccine trials. Dr. Monsonego has received an honorarium as a member of the scientific advisory board of Sanofi Pasteur MSD, Merck & Co, Inc., Roche Diagnostics, Genprobe, and Genticel and compensation from Merck & Co, Inc. and GlaxoSmithKline to conduct vaccine trials. Dr. Muñoz has received an honorarium from Merck & Co, Inc. for being a member of the HPV Global Advisory Board. Dr. Paavonen has received research funding from Merck & Co, Inc. and GlaxoSmithKline through his institution. Dr. Pitisuttihum has received research funding from Merck & Co, Inc. through her institution. Dr. Ronnett has consulted for Merck & Co, Inc. as a member of the Pathology Panel for Merck & Co, Inc. randomized controlled vaccine trials. Dr. Steben has received grants and personal fees from Merck & Co, Inc., BD Diagnostics, Hologic/Gen-Probe, Roche Diagnostics, and Valeant as well as personal fees from Cepheid, Inovio, and Paladin. Dr. Stoler has served or is serving as a consultant in clinical trial design and as an expert pathologist for HPV vaccine and diagnostic trials for Roche, Ventana Medical Systems, Hologic/Gen-Probe, Becton Dickinson, Cepheid, Qiagen, Inovio, and Merck & Co, Inc. Dr. Wheeler has received equipment and reagents for HPV genotyping from Roche Molecular Systems and contracts for HPV vaccine studies from GlaxoSmithKline and Merck & Co, Inc. through her institution, the University of New Mexico. Dr. Wagner is a senior consultant with Analytica LASER, contracted to participate in the analysis, design, and reporting of study findings. Dr. Wiley has received an honorarium as a member of the speakers’ bureau and has received industry-sponsored grant support for research from Merck & Co, Inc. Drs. Perez, Saah, Luxembourg, Li, and Velicer are employees of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc. and hold stock and stock options in the company. Dr. DiNubile was an employee of Merck Sharp & Dohme Corp and held stock and stock options in the company for most of the time this article was in preparation; he continues to hold stock options in the company through 2018 and now is an employee of BioAegis Therapeutics, North Brunswick, New Jersey, where his involvement with the article has continued. The other authors did not report any potential conflicts of interest.
Funding Information:
The research in the current study and the parent studies adhered to Good Publication Practice (GPP3) and was sponsored and funded by Merck & Co, Inc., Kenilworth, New Jersey, the manufacturer of Gardasil and Gardasil9.
PY - 2018
Y1 - 2018
N2 - OBJECTIVE: To estimate the proportion of vulvar and vaginal low-grade and high-grade squamous intraepithelial lesions (LSILs and HSILs) in females 15-26 years of age attributable to 14 human papillomavirus (HPV) genotypes (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59). METHODS: A post hoc analysis of prospectively diagnosed vulvar and vaginal LSILs and HSILs among females 15-26 years of age enrolled in the placebo arms of two phase 3, randomized HPV vaccine trials assessed 14 prespecified HPV genotypes associated with cervical cancers or anogenital warts using a type-specific multiplex polymerase chain reaction assay. The frequency of lesions associated with specific HPV genotypes was estimated by proportional and other attribution methods. RESULTS: During approximately 4 years of follow-up in 8,798 females, 40 vulvar LSILs and 46 vulvar HSILs were diagnosed in 68 females, and 118 vaginal LSILs and 33 vaginal HSILs were diagnosed in 107 females. Females developing vulvar (41.2%) or vaginal (49.5%) lesions also had cervical lesions, whereas 6.5% of females with cervical lesions had vaginal or vulvar lesions. At least 1 of the 14 HPV genotypes was detected in females with vulvar LSIL (72.5%), vulvar HSIL (91.3%), vaginal LSIL (61.9%), and vaginal HSIL (72.7%). Considering only HPV-positive lesions, the nine most common genotypes causing cervical cancer and anogenital warts (6, 11, 16, 18, 31, 33, 45, 52, and 58) were found in 89.4% of vulvar LSILs, 100% of vulvar HSILs, 56.0% of vaginal LSILs, and 78.3% of vaginal HSILs. CONCLUSION: Most vulvar and vaginal lesions were attributable to at least 1 of the 14 HPV genotypes analyzed. Effective immunization programs could potentially prevent substantial numbers of HPV-related vulvar and vaginal LSILs and HSILs.
AB - OBJECTIVE: To estimate the proportion of vulvar and vaginal low-grade and high-grade squamous intraepithelial lesions (LSILs and HSILs) in females 15-26 years of age attributable to 14 human papillomavirus (HPV) genotypes (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59). METHODS: A post hoc analysis of prospectively diagnosed vulvar and vaginal LSILs and HSILs among females 15-26 years of age enrolled in the placebo arms of two phase 3, randomized HPV vaccine trials assessed 14 prespecified HPV genotypes associated with cervical cancers or anogenital warts using a type-specific multiplex polymerase chain reaction assay. The frequency of lesions associated with specific HPV genotypes was estimated by proportional and other attribution methods. RESULTS: During approximately 4 years of follow-up in 8,798 females, 40 vulvar LSILs and 46 vulvar HSILs were diagnosed in 68 females, and 118 vaginal LSILs and 33 vaginal HSILs were diagnosed in 107 females. Females developing vulvar (41.2%) or vaginal (49.5%) lesions also had cervical lesions, whereas 6.5% of females with cervical lesions had vaginal or vulvar lesions. At least 1 of the 14 HPV genotypes was detected in females with vulvar LSIL (72.5%), vulvar HSIL (91.3%), vaginal LSIL (61.9%), and vaginal HSIL (72.7%). Considering only HPV-positive lesions, the nine most common genotypes causing cervical cancer and anogenital warts (6, 11, 16, 18, 31, 33, 45, 52, and 58) were found in 89.4% of vulvar LSILs, 100% of vulvar HSILs, 56.0% of vaginal LSILs, and 78.3% of vaginal HSILs. CONCLUSION: Most vulvar and vaginal lesions were attributable to at least 1 of the 14 HPV genotypes analyzed. Effective immunization programs could potentially prevent substantial numbers of HPV-related vulvar and vaginal LSILs and HSILs.
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U2 - 10.1097/AOG.0000000000002736
DO - 10.1097/AOG.0000000000002736
M3 - Article
C2 - 29995724
AN - SCOPUS:85056609193
SN - 0029-7844
VL - 132
SP - 261
EP - 270
JO - Obstetrics and Gynecology
JF - Obstetrics and Gynecology
IS - 2
ER -