Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study

Silvia de Sanjose, Wim G.V. Quint, Laia Alemany, Daan T. Geraets, Jo Ellen Klaustermeier, Belen Lloveras, Sara Tous, Ana Felix, Luis Eduardo Bravo, Hai Rim Shin, Carlos S. Vallejos, Patricia Alonso de Ruiz, Marcus Aurelho Lima, Nuria Guimera, Omar Clavero, Maria Alejo, Antonio Llombart-Bosch, Chou Cheng-Yang, Silvio Alejandro Tatti, Elena KasamatsuErmina Iljazovic, Michael Odida, Rodrigo Prado, Muhieddine Seoud, Magdalena Grce, Alp Usubutun, Asha Jain, Gustavo Adolfo Hernandez Suarez, Luis Estuardo Lombardi, Aekunbiola Banjo, Clara Menéndez, Efrén Javier Domingo, Julio Velasco, Ashrafun Nessa, Saibua C.Bunnag Chichareon, You Lin Qiao, Enrique Lerma, Suzanne M. Garland, Toshiyuki Sasagawa, Annabelle Ferrera, Doudja Hammouda, Luciano Mariani, Adela Pelayo, Ivo Steiner, Esther Oliva, Chris J.L.M. Meijer, Waleed Fahad Al-Jassar, Eugenia Cruz, Thomas C. Wright, Ana Puras, Cecilia Ladines Llave, Maria Tzardi, Theodoros Agorastos, Victoria Garcia-Barriola, Christine Clavel, Jaume Ordi, Miguel Andújar, Xavier Castellsagué, Gloria I. Sánchez, Andrzej Marcin Nowakowski, Jacob Bornstein, Nubia Muñoz, F. Xavier Bosch

Research output: Contribution to journalArticlepeer-review

2177 Scopus citations

Abstract

Background: Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. Methods: Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. Findings: 22 661 paraffin-embedded samples were obtained from 14 249 women. 10 575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6-50·4], 48·2 years [47·3-49·2], 46·8 years [46·6-48·1], and 55·5 years [54·9-56·1], respectively). Interpretation: To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45. Funding: Spanish grants from Instituto de Salud Carlos III, Agència de Gestió d'Ajuts Universitaris i de Recerca, Marató de TV3 Foundation, and unrestricted grants from GlaxoSmithKline Biologicals, Sanofi Pasteur MSD, and Merck.

Original languageEnglish
Pages (from-to)1048-1056
Number of pages9
JournalThe Lancet Oncology
Volume11
Issue number11
DOIs
StatePublished - Nov 2010
Externally publishedYes

Bibliographical note

Funding Information:
YLQ has received support for travel to meetings for the study or other purposes (personal) from MSD and GlaxoSmithKline. GAHS has received an independent grant from MSD for epidemiological study related to genital warts in Colombia; and payments from MSD for travel accommodation at the International HPV conference in Canada, 2011. NM has received payment for board membership (personal) from Merck, and for lectures (personal) from Merck and Sanofi Pasteur. AMN has received payment for board membership (personal) and consultancy (personal) from GlaxoSmithKline, and for lectures (personal) from GlaxoSmithKline and MSD. CJLMM has received payment for board membership (institution) from Qiagen until 2009; payment for consultancy from Qiagen (institution); payment for lectures including service on speakers bureaus (institution) from Roche and GlaxoSmithKline; payment for patents (institution) from Qiagen for HPV detection by gp5+/6+; royalties (institution) from Oncomethylome Sciences for a patent on promoter methylation of Technological Support for Strategy, Learning and Change specific marker for cervical intraepithelial neoplasia 2+2005; and travel, accommodations, or meeting expenses (personal) from Qiagen and Roche. TCW has received payment for consultancy (personal) from Merck, GlaxoSmithKline, GenProbe, and Roche Molecular Diagnostics; and for lectures including service on speakers bureaus (personal) from Merck, GlaxoSmithKline, and Roche Molecular Diagnostics. SDS has received payment for consultancy (personal) from Qiagen, and for lectures including service on speakers bureaus (personal) from Qiagen, Sanofi, and GlaxoSmithKline. LA has received support for travel to meetings for the study or other purposes (institutional) from Sanofi Pasteur MSD. NG has received institutional support for occasional travel by GlaxoSmithKline and Merck. FXB has received payment for consultancy (personal) from MSD Internal Steering Committee; payment for expert testimony (personal) from GlaxoSmithKline Food and Drug Administration and EMEA clinical expert; and grants (institution) from GlaxoSmithKline, MSD, and Sanofi Pasteur MSD for epidemiological studies; payment for development of educational presentations (institution) from GlaxoSmithKline; travel, accommodations, and meeting expenses (personal) from GlaxoSmithKline and Sanofi Pasteur MSD. JB has received a grant (institution) from MSD Israel for a research assistant working with the pathology laboratory staff, assisting in the assembly and transport of paraffin blocks; consultancy (personal) payments from MSD Israel; and payment for lectures, including service on speakers bureaus (personal) from GlaxoSmithKline Israel. GIS has received a study grant (institution) from Marató de TV3 Foundation, and grants (institution) from Merck. XC has received a study grant (institution) from Sanofi Pasteur MSD and Merck; consultancy payments from Sanofi Pasteur MSD, and GlaxoSmithKline; grants (institution) from GlaxoSmithKline, Merck, Sanofi Pasteur MSD; and payment for lectures including service on speakers bureaus (personal) from GlaxoSmithKline and Sanofi Pasteur MSD. BL has received payment for lectures including service on speakers bureaus (personal) from Roche and Qiagen. SAT has received payment for lectures including service on speakers bureaus from MSD; and travel, accommodations, or meeting expenses from Merck. SMG has received board membership from GlaxoSmithKline, Commonwealth Serum Laboratories advisory board for cervical cancer vaccine; payment for development of education presentations from GlaxoSmithKline, EXCEL program; grants have been paid to SMG's institute by the Royal Women's Hospital Melbourne. CC has received payment for consultancy from Merck (steering committee about HPV vaccination), expert testimony from Roche, and funding for travel from Sanofi Pasteur, MSD, and GlaxoSmithKline. CLL has received institutional grants from GlaxoSmithKline. The other authors declared no conflicts of interest.

Funding Information:
The study has been partly supported by Spanish public grants from the Instituto de Salud Carlos III (grants numbers FIS PI030240, FIS PI061246, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095 , and CIBERESP ), Agència de Gestió d'Ajuts Universitaris i de Recerca ( AGAUR 2005SGR 00695 and 2009SGR126 ), Marató de TV3 Foundation ( 051530 ), and GlaxoSmithKline Biologicals, Sanofi Pasteur MSD, and Merck. The contribution of Cristina Rajo in the preparation of the report is recognised.

Funding

YLQ has received support for travel to meetings for the study or other purposes (personal) from MSD and GlaxoSmithKline. GAHS has received an independent grant from MSD for epidemiological study related to genital warts in Colombia; and payments from MSD for travel accommodation at the International HPV conference in Canada, 2011. NM has received payment for board membership (personal) from Merck, and for lectures (personal) from Merck and Sanofi Pasteur. AMN has received payment for board membership (personal) and consultancy (personal) from GlaxoSmithKline, and for lectures (personal) from GlaxoSmithKline and MSD. CJLMM has received payment for board membership (institution) from Qiagen until 2009; payment for consultancy from Qiagen (institution); payment for lectures including service on speakers bureaus (institution) from Roche and GlaxoSmithKline; payment for patents (institution) from Qiagen for HPV detection by gp5+/6+; royalties (institution) from Oncomethylome Sciences for a patent on promoter methylation of Technological Support for Strategy, Learning and Change specific marker for cervical intraepithelial neoplasia 2+2005; and travel, accommodations, or meeting expenses (personal) from Qiagen and Roche. TCW has received payment for consultancy (personal) from Merck, GlaxoSmithKline, GenProbe, and Roche Molecular Diagnostics; and for lectures including service on speakers bureaus (personal) from Merck, GlaxoSmithKline, and Roche Molecular Diagnostics. SDS has received payment for consultancy (personal) from Qiagen, and for lectures including service on speakers bureaus (personal) from Qiagen, Sanofi, and GlaxoSmithKline. LA has received support for travel to meetings for the study or other purposes (institutional) from Sanofi Pasteur MSD. NG has received institutional support for occasional travel by GlaxoSmithKline and Merck. FXB has received payment for consultancy (personal) from MSD Internal Steering Committee; payment for expert testimony (personal) from GlaxoSmithKline Food and Drug Administration and EMEA clinical expert; and grants (institution) from GlaxoSmithKline, MSD, and Sanofi Pasteur MSD for epidemiological studies; payment for development of educational presentations (institution) from GlaxoSmithKline; travel, accommodations, and meeting expenses (personal) from GlaxoSmithKline and Sanofi Pasteur MSD. JB has received a grant (institution) from MSD Israel for a research assistant working with the pathology laboratory staff, assisting in the assembly and transport of paraffin blocks; consultancy (personal) payments from MSD Israel; and payment for lectures, including service on speakers bureaus (personal) from GlaxoSmithKline Israel. GIS has received a study grant (institution) from Marató de TV3 Foundation, and grants (institution) from Merck. XC has received a study grant (institution) from Sanofi Pasteur MSD and Merck; consultancy payments from Sanofi Pasteur MSD, and GlaxoSmithKline; grants (institution) from GlaxoSmithKline, Merck, Sanofi Pasteur MSD; and payment for lectures including service on speakers bureaus (personal) from GlaxoSmithKline and Sanofi Pasteur MSD. BL has received payment for lectures including service on speakers bureaus (personal) from Roche and Qiagen. SAT has received payment for lectures including service on speakers bureaus from MSD; and travel, accommodations, or meeting expenses from Merck. SMG has received board membership from GlaxoSmithKline, Commonwealth Serum Laboratories advisory board for cervical cancer vaccine; payment for development of education presentations from GlaxoSmithKline, EXCEL program; grants have been paid to SMG's institute by the Royal Women's Hospital Melbourne. CC has received payment for consultancy from Merck (steering committee about HPV vaccination), expert testimony from Roche, and funding for travel from Sanofi Pasteur, MSD, and GlaxoSmithKline. CLL has received institutional grants from GlaxoSmithKline. The other authors declared no conflicts of interest. The study has been partly supported by Spanish public grants from the Instituto de Salud Carlos III (grants numbers FIS PI030240, FIS PI061246, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095 , and CIBERESP ), Agència de Gestió d'Ajuts Universitaris i de Recerca ( AGAUR 2005SGR 00695 and 2009SGR126 ), Marató de TV3 Foundation ( 051530 ), and GlaxoSmithKline Biologicals, Sanofi Pasteur MSD, and Merck. The contribution of Cristina Rajo in the preparation of the report is recognised.

FundersFunder number
CIBERESP
GlaxoSmithKline Biologicals
GlaxoSmithKline
Merck
Fundació la Marató de TV3051530
Sanofi Pasteur
Agència de Gestió d'Ajuts Universitaris i de Recerca2009SGR126, 2005SGR 00695
Instituto de Salud Carlos IIIFIS PI030240, RCESP C03/09, FIS PI061246, RTIC RD06/0020/0095, RTICESP C03/10

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