Original articleCervical intraepithelial neoplasia grade 2 or worse in Galicia, Spain: HPV 16 prevalence and vaccination impactNeoplasia intraepitelial cervical de grado 2 o peor en Galicia (España): prevalencia de HPV 16 e impacto vacunal
Introduction
The knowledge of a 99.7% worldwide HPV prevalence in cervical carcinomas1 and the fact that persistence of a high risk human papillomavirus (HR-HPV) infection is essential for the development, maintenance and progression of high-grade cervical intraepithelial neoplasia (CIN)2, 3 have changed cervical cancer prevention. Several longitudinal, randomized-controlled trials4, 5, 6 have demonstrated improved prevention of high-grade CIN and cervical cancer with the introduction of HPV testing in cervical screening. In the particular case of Galicia (Spain), an organized cervical cancer screening protocol was introduced by Galician Public Health Service in 2008 according to European and National recommendations (www.sergas.es). In brief, it was a Pap-based screening program. In case of detection of low-grade or high-grade cytological alterations women were referred to colposcopy. The HPV DNA testing was used as a triage test for colposcopy referral in case of atypical squamous cells of undetermined significance (ASC-US) in women older than 25 years of age.
Two HPV vaccines, namely Merck’ Gardasil® and GSK’ Cervarix®, approved by Federal Drug Administration (FDA) in 2006–2007 protect against acquisition of infections with oncogenic HPV types 16 and 18 and their lesions,7, 8 which are responsible for about 70% of all cervical cancers.9 In September of 2008, free vaccination of girls aged 14 years against HPV 16 and 18 with the bivalent vaccine was introduced in Galicia (Spain). The impact of the vaccination on cervical cancer incidence is expected to take several decades to manifest itself.
The implementation of any new intervention requires surveillance in the general population to measure its efficacy. To provide a baseline HPV-type specific prevalence in precancerous and cancerous cervical lesions is essential for future comparisons in order to evaluate the impact of screening protocols and vaccination in cervical cancer prevention.
In this way, a retrospective study was performed in order to know the HPV prevalence in histologically confirmed cases of moderate-grade CIN or worse (CIN2+) which were detected in Galicia, Spain, prior to widespread HPV vaccination, the expected impact of bivalent vaccination in these cervical lesions and the distribution of HPV 16 in squamous lesions.
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Patients, ethical statement and epidemiological data
We conducted a retrospective study including consecutive cases of CIN2+ diagnosed during 2009–2010 in women attending the Gynecological Unit of Meixoeiro Hospital (University Hospital of Vigo, Galicia, Spain) for cervical cancer screening. Women had not been vaccinated with any HPV vaccine at time of diagnosis. Ninety-four women agreed to be enrolled.
This study received approval from the ethics committee of clinical investigation of Galicia (Santiago de Compostela, Spain). All study
Results
A total of 94 women between 18 and 82 years of age at CIN2+ diagnosis time (mean age 37.5 years. 95% CI, 35.1–39.8) were included in this study. Histological diagnoses were: CIN2 (n = 23), CIN3-CIS (n = 58), AIS (n = 5) and SCC (n = 8). Presence of HR-HPV was detected in 91/94 (96.8%) CIN2+ cases: 43 (47%) single infections and 48 (53%) multiple infections. Type-specific prevalence is shown in Table 2. HPV 16 and 31 were the most frequent genotypes in single and multiple infections. Genotypes other
Discussion
This study provides data for the local distribution of HPV genotypes among unvaccinated women with CIN2+ in Galicia, Spain. This knowledge could be useful for future evaluations of the impact of the bivalent vaccination that was introduced recently, allow identification of local problems of primary or secondary prophylaxis, of HPV transmission and special needs of Public Health Service interventions.
The data confirmed that HPV 16 is found in the majority of cervical dysplasia, especially in
Conclusions
Although HPV 16 is the most frequent genotype in CIN2+, other genotypes not included in the vaccine like HPV 31, 33, 35, 45, 51, 52, 56 and 58 are also common, suggesting that the development of new vaccines against a higher number of genotypes is important. HPV vaccination could have a great impact in women younger than 45 years of age because of the high prevalence of HPV 16 in their lesions. Presence of multiple high-risk genotypes in CIN2+ might influence the vaccination impact.
Funding
This work was supported by Conselleria de Sanidade, Galicia, Spain.
Conflict of interest
The authors declare no conflict of interest.
Acknowledgements
We thank Malvar A (Department of Epidemiology, Galician Public Health Service, Spain) for critical review of the manuscript. We thank Biomedical Foundation of the University Hospital of Vigo, Spain for the statistical analysis and the English revision of the manuscript. We are also grateful to Taboada P (Peixe Software, SLNE, Spain) for the online software donation for data collection.
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