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


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
Issue number11
Publication statusPublished - Nov 2010

ASJC Scopus subject areas

  • Oncology


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