Cervical HPV type-specific pre-vaccination prevalence and age distribution in Croatia

PLOS ONE, Dec 2019

The main etiological factor of precancerous lesion and invasive cervical cancer are oncogenic human papillomaviruses types (HPVs). The objective of this study was to establish the distribution of the most common HPVs in different cervical lesions and cancer prior to the implementation of organized population-based cervical screening and HPV vaccination in Croatia. In this study, 4,432 cervical specimens, collected through a 16-year period, were tested for the presence of HPV-DNA by polymerase chain reaction (PCR) with three sets of broad-spectrum primers and type-specific primers for most common low-risk (LR) types (HPV-6, 11) and the most common high-risk (HR) types (HPV-16, 18, 31, 33, 45, 52, 58). Additional 35 archival formalin-fixed, paraffin embedded tissue of cervical cancer specimens were analyzed using LiPA25 assay. The highest age-specific HPV-prevalence was in the group 18–24 years, which decreased continuously with age (P<0.0001) regardless of the cytological diagnosis. The prevalence of HR-HPV types significantly increased (P<0.0001) with the severity of cervical lesions. HPV-16 was the most common type found with a prevalence (with or without another HPV-type) of 6.9% in normal cytology, 15.5% in atypical squamous cells of undetermined significance, 14.4% in low-grade squamous intraepithelial lesions, 33.3% in high-grade squamous intraepithelial lesions, and 60.9% in cervical cancer specimens (P<0.0001). This study provides comprehensive and extensive data on the distribution of the most common HPV types among Croatian women, which will enable to predict and to monitor the impact of HPV-vaccination and to design effective screening strategies in Croatia.

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Cervical HPV type-specific pre-vaccination prevalence and age distribution in Croatia

July Cervical HPV type-specific pre-vaccination prevalence and age distribution in Croatia Ivan Sabol 0 1 Nina Milutin GasÏ perov 0 1 Mihaela Matovina 0 1 Ksenija BozÏinović 0 1 Goran GrubisÏ ić 1 Ivan Fistonić 1 Dragan Belci 1 Laia Alemany 1 2 Sonja DzÏebro 1 Mara Dominis 1 Mario SÏekerija 1 Sara Tous 1 2 Silvia de Sanjose 1 2 Magdalena Grce 0 1 0 Department of Molecular Medicine, Ruđer BosÏković Institute, Zagreb, Croatia, 2 University Hospital Sisters of Mercy, Clinic of Obstetrics and Gynaecology , Zagreb, Croatia, 3 Obstetrics , Gynecology and Menopause Clinic , Zagreb , Croatia , 4 Department of Gynecology and Obstetrics, General Hospital Pula , Pula , Croatia 1 Editor: Maria Lina Tornesello, Fondazione IRCCS Istituto Nazionale dei Tumori , ITALY 2 Cancer Epidemiology Research Program, Unit of Infections and Cancer, Catalan Institute of Oncology, Barcelona , Spain, 6 CIBER en EpidemiologÂõa y Salud Pu blica (CIBERESP), Barcelona , Spain , 7 Department of Pathology and Cytology, University of Zagreb, School of Medicine, University Hospital Merkur, Zagreb, Croatia, 8 Croatian National Cancer Registry, Croatian Institute of Public Health , Zagreb , Croatia , 9 School of Medicine, Andrija SÏtampar School of Public Health, University of Zagreb , Zagreb , Croatia The main etiological factor of precancerous lesion and invasive cervical cancer are oncogenic human papillomaviruses types (HPVs). The objective of this study was to establish the distribution of the most common HPVs in different cervical lesions and cancer prior to the implementation of organized population-based cervical screening and HPV vaccination in Croatia. In this study, 4,432 cervical specimens, collected through a 16-year period, were tested for the presence of HPV-DNA by polymerase chain reaction (PCR) with three sets of broad-spectrum primers and type-specific primers for most common low-risk (LR) types (HPV-6, 11) and the most common high-risk (HR) types (HPV-16, 18, 31, 33, 45, 52, 58). Additional 35 archival formalin-fixed, paraffin embedded tissue of cervical cancer specimens were analyzed using LiPA25 assay. The highest age-specific HPV-prevalence was in the group 18±24 years, which decreased continuously with age (P<0.0001) regardless of the cytological diagnosis. The prevalence of HR-HPV types significantly increased (P<0.0001) with the severity of cervical lesions. HPV-16 was the most common type found with a prevalence (with or without another HPV-type) of 6.9% in normal cytology, 15.5% in atypical squamous cells of undetermined significance, 14.4% in low-grade squamous intraepithelial lesions, 33.3% in high-grade squamous intraepithelial lesions, and 60.9% in cervical cancer specimens (P<0.0001). This study provides comprehensive and extensive data on the distribution of the most common HPV types among Croatian women, which will enable to predict and to monitor the impact of HPV-vaccination and to design effective screening strategies in - Data Availability Statement: All relevant data are within the paper. Funding: This research has been partially supported by the Croatian Ministry of Science, Education and Sports (grant no. 098-09824642510, URL: zprojekti.mzos.hr), and partially by the international project ºRetrospective International Survey and HPV Time Trends Study Groupº (URL: ico.gencat.cat). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There Croatia. was no additional external funding received for this study. Introduction Cervical cancer represents an important public health issue in Croatia where it is the ninth most common type of cancer in women, and also ninth most common cause of cancer death [ 1 ]. Each year in Croatia, over 300 women develop cervical cancer and approximately 130 women die from this disease. According to the latest data for Croatia, in 2014 there were 307 new cases (world age-standardized incidence rate (ASR-W) 11.9/100,000 women-years/WY), and in the same year 130 women died from cervical cancer (ASR-W 4.4/100,000 WY). In Europe, cervical cancer is estimated to be the sixth most common cancer in women in 2012, with almost 60,000 new cases per year (3.6% of all incident cancers; 11.4 ASR-W) [ 2,3 ]. Since the introduction of the opportunistic cervical cancer screening in Croatia trends of cervical cancer rates were declining as shown from 1968 to 2014 on Fig 1 [ 1 ]. The trends in the cervical cancer mortality rates in Croatia remained at a low level but no decrease was observed over the last two decades (Fig 1). Age-specific incidence rates of cervical cancer in Croatia was unchanged from 1988 to 2013,showing two distinctive peaks with the highest rate at age 50 and 75 [ 1 ]. Moreover, the results from EUROCARE-5 [ 4 ], a study on cancer 5-year relative survival in Europe, showed that Croatia is a little bit above average (65.1% vs. 62.4%) when compared to other European countries. Based o (...truncated)


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Ivan Sabol, Nina Milutin Gašperov, Mihaela Matovina, Ksenija Božinović, Goran Grubišić, Ivan Fistonić, Dragan Belci, Laia Alemany, Sonja Džebro, Mara Dominis, Mario Šekerija, Sara Tous, Silvia de Sanjosé, Magdalena Grce. Cervical HPV type-specific pre-vaccination prevalence and age distribution in Croatia, PLOS ONE, 2017, Volume 12, Issue 7, DOI: 10.1371/journal.pone.0180480