Human Papillomavirus Type Distribution in Cervical Intraepithelial Neoplasia Grade 2/3 and Cervical Cancer in Portugal: A CLEOPATRE II Study

Pista, Angela PhD*; de Oliveira, Carlos Freire PhD, MD; Lopes, Carlos PhD, MD; Cunha, Maria João MD§; on behalf of the CLEOPATRE Portugal Study Groupa

International Journal of Gynecological Cancer: March 2013 - Volume 23 - Issue 3 - p 500–506
doi: 10.1097/IGC.0b013e318280f26e
Cervical Cancer

Objective: Cervical cancer is the third most frequent cancer in women, worldwide and etiologically associated with infection by human papillomavirus (HPV). Following the results of the first epidemiologic population-based CLEOPATRE study in Portugal, it was important to understand the HPV type-specific distribution in women with cervical intraepithelial neoplasia (CIN) grades 2 and 3 and invasive cervical cancer (ICC).

Methods: This was an observational, multicenter, cross-sectional study with retrospective data collection. Between January 2008 and May 2009, paraffin-embedded samples of histologically confirmed cases of CIN2, CIN3, and ICC were collected from the 5 regional health administrations in mainland Portugal. Eligible samples were sent to 2 central laboratories for histological reassessment and HPV genotyping. Prevalence estimates were calculated together with 95% confidence intervals.

Results: A total of 582 samples, 177 cases of CIN2, 341 of CIN3, and 64 of ICC, were included. The mean age of participants was 41.8 years (range, 20–88 years). The overall HPV prevalence was 97.9% with a higher prevalence of high-risk genotypes, particularly HPV 16. Multiple infections were observed in 11.2% of the cases. Human papillomavirus prevalence was 95.5% in CIN2, 99.4% in CIN3, and 96.9% in ICC. The 8 more frequent genotypes in order of decreasing frequency were HPV 16, 31, 58, 33, 51, 52, 18, and 35 in CIN2 and HPV 16, 31, 33, 58, 52, 35, 18, and 51 in CIN3. In ICC cases, the 12 detected HPV genotypes were HPV 16, 18, 31, 33, 45, 51, 52, 53, 56, 58, 59, and 73. However, HPV 53 and 73 were always associated to other high-risk genotypes. Human papillomavirus types 31, 51, 52, 56, and 59 were detected in 1 case each.

Conclusions: Human papillomavirus prevalence and patterns of type-specific HPV positivity were comparable with other studies. Current HPV vaccines should protect against HPV genotypes responsible for 77.4% of ICC in Portugal.

*National Institute of Health, Lisbon; †Federation for the Gynaecological and Obstetrician Societies, Coimbra; ‡Abel Salazar Biomedical Sciences Institute, Oporto; and §Scientific Department of Sanofi Pasteur MSD-Portugal, Amadora, Portugal.

Address correspondence and reprint requests to Angela Pista, PhD, Instituto Nacional de Saúde, Avenida Padre Cruz, 1649-016 Lisboa, Portugal. E-mail:

This study was sponsored by Sanofi Pasteur MSD.

M.J.C. is an SPMSD employee; C.F.d.O. and A.P. received travel grant and hotel expenses from SPMSD Portugal; C.L. received travel grant and hotel expenses from SPMSD Portugal.

The authors take full responsibility for the content of this contribution. The CLEOPATRE Portugal study coordinators (A.P., C.F.d.O., C.L., M.J.C.) were involved in the study design, database analyses, and preparation/review of the article.

aCLEOPATRE Portugal Study Group members and coauthors: CENTRO HOSPITALAR DE VILA NOVA DE GAIA: Angelina Tavares; Macedo Dias; Eugénia Rocha. HOSPITAL CUF DESCOBERTAS: Maria da Conceição Telhado; Ana Afonso; Mariana Loureiro; Cristina Horgan; Idalina Marques; Elisete Cortes; Sofia Alegra; Maria do Carmo Serra; Jorge Lima; Elisabete Afonso (administrative support). HOSPITAL DE BEJA: Ana Paula Ladeira; Luis Gonçalves; Naciolinda Sobral; Ana Sofia Reforço (administrative support). HOSPITAL DE FARO: Maria Amália Pacheco; José Luis Enriquez; António Lagoa; Vera Ribeiro; Leonor Ferreira; António Jesús Cadillá. HOSPITAL DE GUIMARÃES: José Manuel Furtado; Joaquim Rodrigues; Pedro Vieira de Castro; António Almeida e Silva. HOSPITAIS DA UNIVERSIDADE DE COIMBRA: Fernando Mota; Paulo Moura; Teresa Simões da Silva; Ondina Jardim; Maria Nascimento. MATERNIDADE ALFREDO DA COSTA: Jorge Borrego; Rosário Fernandes; Adelaide Vitorino; Teresa Paula; Fátima Palma; Paula Maia; Ana Fatela; Daniela Sobral; Paula Pereira; Isabel Grilo; Paula Ambrósio; Isabel Torrezão; Isabel Biscaia; Sílvia Nunes; Mariana Araújo; Susana Sâncio; Gisela Valente (nurs e); Sara Mendonça (nurse). INSTITUTO NACIONAL DE SAÚDE—Papillomavirus Laboratory: Nuno Verdasca; Ana Oliveira; SANOFI PASTEUR MSD-PORTUGAL: Sofia Santos (administrative support).

The authors declare no conflicts of interest.

Received November 15, 2012

Accepted December 2, 2012

Copyright © 2013 by IGCS and ESGO