Clinical trial NCT01385436: Distribution of Human Papillomavirus (HPV) Genotypes in Patients With Cervical Cancer From Croatia
Official title: Pre-vaccination Distribution of Human Papillomavirus (HPV) Genotypes in Patients With High Grade Cervical Squamous Intraepithelial Lesion (HSIL) and Cervical Cancer From Croatia
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cervical Cancer
Keywords: human papillomavirus (HPV)
cervical cancer
high grade cervical squamous intraepithelial lesion (HSIL)
Lead sponsor: University Hospital for Infectious Diseases, Croatia
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2011-06-30
Enrollment: 400
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Women aged 18-65 with a cytological diagnosis of CIN2+cervical lesions from all over Croatia that are referred to the National Reference Center because of HSIL or malignant cytology findings.

Brief summary: Human papillomavirus (HPV) of high-risk genotype is a necessary risk factor in development of cervical cancer. There is a vaccine available to prevent cervical lesions associated with high-risk HPV genotypes 16 and 18. In Croatia HPV vaccination has not yet been introduced in obligatory vaccination schedule. The aim of this study is to describe the pre-vaccination distribution of HPV genotypes in women with high grade cervical squamous intraepithelial lesion (HSIL) and cervical cancer in Croatia. The investigators hypothesis is that HPV-16 is the most frequently found genotype but the distribution of other HPV genotypes is heterogeneous and includes genotypes currently not covered by vaccination.

Detailed description: This is a single-center cross-sectional study on the molecular virology of human papillomavirus (HPV) in Croatia. The study will enroll women aged 18-65 years of age with cervical intraepithelial neoplasia (CIN2+)cervical lesions that received clinical care at the Croatian Center for Pre-malignant and Malignant Diseases of the Cervix. Women with abnormal cytology (high grade cervical squamous intraepithelial lesion-HSIL, cervical cancer) in the period from 2010 to 2012 will be included. Relevant epidemiological and clinical data will be collected. Biological samples will include both biopsy specimens from cervix and cervical swab. Biological samples will be put in Digene Specimen Transport Medium (Qiagen, Gaithersburg, MD) and further analyzed at the Department of Molecular Diagnostics at the University Hospital for Infectious Diseases in Zagreb. HPV genotyping will be performed by using a standardized molecular assay INNO-LiPA HPV Genotyping Extra Test (Solvay S.A., Brussels, Belgium). Analysis of genomic variants of HPV 16 genotype will be performed by population-based sequencing of L1 genome region.

Eligibility criteria: Inclusion Criteria:

* Women aged 18-65 with a cytological diagnosis of CIN2+cervical lesions from all over Croatia that are referred to National Reference Center because of HSIL or malignant cytology findings

Exclusion Criteria:

* Women younger than 18 or older than 65
* Pregnant women

Primary outcomes:
measure: Pre-vaccination distribution of HPV genotypes in women with HSIL and invasive cervical carcinoma
timeFrame: two years
Secondary outcomes:
measure: HPV vaccine coverage in Croatia
timeFrame: two years
Other outcomes:
Locations:
city: Zagreb
country: Croatia
facility: University Hospital for Infectious Diseases, Croatia
Study officials:
affiliation: University Hospital for Infectious Diseases Zagreb, Croatia
name: Adriana Vince, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Milutin Gasperov N, Sabol I, Matovina M, Spaventi S, Grce M. Detection and typing of human papillomaviruses combining different methods: polymerase chain reaction, restriction fragment length polymorphism, line probe assay and sequencing. Pathol Oncol Res. 2008 Dec;14(4):355-63. doi: 10.1007/s12253-008-9084-2. Epub 2008 Aug 28.
citation: Lepej SZ, Grgic I, Poljak M, Iscic-Bes J, Skerk V, Vince DB, Dusek D, Vince A. Detection of human papillomavirus genotypes 16/18/45 by hybrid capture hybridisation genotyping probe in clinical specimens: the first report. J Clin Virol. 2007 Oct;40(2):171-2. doi: 10.1016/j.jcv.2007.07.002. Epub 2007 Aug 16. No abstract available.
citation: Seme K, Lepej SZ, Lunar MM, Iscic-Bes J, Planinic A, Kocjan BJ, Vince A, Poljak M. Digene HPV Genotyping RH Test RUO: comparative evaluation with INNO-LiPA HPV Genotyping Extra Test for detection of 18 high-risk and probable high-risk human papillomavirus genotypes. J Clin Virol. 2009 Oct;46(2):176-9. doi: 10.1016/j.jcv.2009.07.017. Epub 2009 Aug 15.
citation: Vrtacnik Bokal E, Kocjan BJ, Poljak M, Bogovac Z, Jancar N. Genomic variants of human papillomavirus genotypes 16, 18, and 33 in women with cervical cancer in Slovenia. J Obstet Gynaecol Res. 2010 Dec;36(6):1204-13. doi: 10.1111/j.1447-0756.2010.01316.x.
citation: Poljak M, Kocjan BJ. Commercially available assays for multiplex detection of alpha human papillomaviruses. Expert Rev Anti Infect Ther. 2010 Oct;8(10):1139-62. doi: 10.1586/eri.10.104.