Human papillomavirus genotype distribution in cervical cancer cases in Spain. Implications for prevention
Highlights
► In Spain, 72.4% of cervical cancers can be attributed to HPV16/18; and, particularly, in adenocarcinomas up to a 94%. ► In the last 60 years, HPV16/18 relative contribution has been stable. ► Our results suggest a major impact of HPV vaccines on cervical cancer reduction in Spain.
Introduction
Since the identification of human papillomavirus (HPV) as the necessary cause of cervical cancer and, consequently, the development of new HPV-based preventive measures (HPV vaccines and HPV screening tools), cervical cancer has become an almost entirely preventable disease [1], [2].
Spain is a country in the south of Europe with low incidence and mortality rates of cervical cancer (age-standardized rates of 6.3 and 1.9 per 100,000 women, respectively) [3]. For many years, health governments of the different Spanish regions have devoted substantial resources for cervical cancer prevention through screening. In spite of these efforts, the large majority of current screening protocols in the 17 Spanish autonomous communities are still opportunistic cytology-based programs, with an estimated coverage ranging from 40% to 80% in women in between 18 and 70 years of age (% of female self-reporting at least one cytology in last three years) [4], [5], [6], [7]. Data from Spanish cancer registries suggest that there has been no clear impact on cervical cancer incidence rates over the last decades [8]. Recently, few regions have introduced HPV testing as ancillary and triage tool in screening. As an example, the autonomous community of Catalonia has introduced HPV-testing adjuvant to cytology in cervical cancer screening of women aged over 40 years with a poor screening history identified as those with absence of a pap smear in the previous 5 years [9]. Since 2008–09, each year a cohort of girls within the age range of 11–14 years are vaccinated against HPV infection free of direct charge, through school-based programs or primary care centers. The global estimate of the HPV vaccine coverage rate of the three doses of the first vaccinated cohort was of 77.2% (ranging from 62.2% in Andalucia to 97.4% in La Rioja) [10].
An analysis from Diaz et al. [11] has shown that in Spain strategies that include both pre-adolescent vaccination (under a theoretical 100% vaccine coverage) and screening (starting at 25 years) are more effective than vaccination or screening alone.
Information on HPV genotype distribution in invasive cervical cancer (ICC) as opposed to the distributions typically found in pre-invasive disease or in populations with normal cytology is critical in order to estimate the impact of the inclusion of HPV vaccination as part of the preventive strategy. In Spain, there is scarce information regarding HPV type-specific distribution in women with ICC [12].
We present a thorough analysis of the HPV genotype distribution of ICC cases from six Spanish regions with the purpose of quantifying the contribution of the vaccine HPV types in ICC from Spain in a pre-vaccination period.
Section snippets
Study design and materials
The project was designed and coordinated by the Catalan Institute of Oncology (ICO) in Barcelona, Spain and the DDL Laboratories in Voorburg, The Netherlands. The study is part of an international retrospective prevalence survey of HPV DNA types in cervical cancer [13]. The Spanish collaborating centers originated from six autonomous communities: Asturias (Hospital San Agustín & IUOPA, Avilés); Canarias (Complejo Hospitalario Universitario Insular Marteno-Infantil, Las Palmas de Gran Canaria);
Results
Overall 1311 cervical cancer cases were recruited. After histopathological verification 268 samples were excluded (20.4%), thus 1043 were finally included as suitable for HPV analysis. Reasons for exclusion were: no invasive cancer in the specimen (n = 231), biopsy obtained from metastasis (n = 4) and cancer of no cervical origin (n = 33). Cases were diagnosed between 1940 up to 2007 and had an average age at diagnosis of 56.2 years (Standard Deviation-SD: 15.3 y). However, information on age was
Discussion
This work confirms that HPV 16 is the major HPV type involved in ICC in Spain, and that HPV 16 and HPV 18 contribute to 72.4% (95% CI: 69.3%–75.2%) of all HPV DNA positive cases. This is the largest series of invasive cervical cancer cases derived from Spain. The results are in accordance with the international data [13], [17]. The eight most common types worldwide recently reported [13], HPV 16, 18, 31, 33, 35, 45, 52 and 58 were also the commonest types in Spain with the exception of HPV 56
Conflict of interest statement
LA: Has received occasional support for travel to meetings for the study or other purposes (institutional) from Sanofi Pasteur MSD.
BLL: Has received payment for lectures including service on speaker's bureaus (personal) and support for occasional travel from Roche, Qiagen and Innogenetics.
NG: Has received institutional support for occasional travel by GlaxoSmithKline and Merck Sharp & Dohme.
XC: Has received occasional travel fund to attend scientific meetings and honorarium for lectures by
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2023, Gynecology and Obstetrics Clinical MedicineInfection status and survival impact of high-risk human papillomavirus in cervical adenocarcinomas: A systematic review and meta-analysis
2022, Gynecologic OncologyCitation Excerpt :Finally, 71 studies with 11,225 participants were included in the HPV infection analysis and 8 studies with 1099 participants in the prognosis analysis. The general characteristics of the studies included in the HPV infection analysis were summarized in Supplementary Table 1 [6,15–84]. High-risk types include HPV-16, −18, −26, −30, −31, −33, −35, −39, −45, −51, −52, −56, −58, −59, −66, −68, −69, −73 and − 82, and low-risk types include HPV-6, −11, −34, −40, −42, −43, −44, −54, −61 and − 72 [18,85].
Prevention of infectious diseases. PAPPS update on vaccines for 2018
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Enrique Lerma (Hospital de la Santa Creu i Sant Pau, Barcelona); Antonio Llombart-Bosch, Morelva Toro (Facultad de Medicina, Universidad de Valencia); Belen Lloveras (Hospital del Mar, Barcelona); Ana Puras, Rosa Guarch (Hospital Virgen del Camino, Pamplona); Miguel Andújar (Complejo Hospitalario Universitario Insular Marteno-Infantil, Las Palmas de Gran Canaria); Jaume Ordi (CRESIB (Centre de Recerca en Salut Internacional de Barcelona) Hospital Clínic-University of Barcelona, Barcelona); Adela Pelayo (Hospital Clínico San Carlos, Madrid); Julio Velasco, Cristina Pérez (Hospital San Agustín, & IUOPA (Oncologic and Universitary Institute of Principality of Asturias)); Maria Alejo (Hospital General de l'Hospitalet de Llobregat, Barcelona); Laia Alemany, F. Xavier Bosch, Vanesa Camón, Xavier Castellsagué, Omar Clavero, Silvia de Sanjosé, Ana Esteban, Nuria Guimerà, Yolanda Florencia, Joellen Klaustermeier, Nubia Muñoz, Bea Quirós, Cristina Rajo, Sara Tous, Marleny Vergara (IDIBELL, Institut Català d'Oncologia-Catalan Institute of Oncology, Hospitalet de Llobregat, Barcelona).