Abstract
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.
Highlights
Cervical cancer represents an important public health issue in Croatia where it is the ninth most common type of cancer in women, and ninth most common cause of cancer death [1]
Similar findings were reported by other recent studies; summary of 18 studies from 14 European countries indicated that human papillomaviruses types (HPVs)-16 is the most prevalent HPV-type, found in 29.8% of HPV-positive samples [26]
The world-wide meta-analysis of distribution of HPV-types, points out HPV-16, as the most prevalent type, whose presence is steadily increasing with the severity of the cytological changes, from normal cytology (20.4% +/- 3.6%), to ASCUS (22.9% +/- 2.9%), LSIL (25.1% +/- 2.8%), and HSIL (47.5% +/- 5.5%), and being the highest in ICC (62.6 +/- 2.2) [27]
Summary
Cervical cancer represents an important public health issue in Croatia where it is the ninth most common type of cancer in women, and 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]. 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]. 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
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