Clinical trial NCT00937547: Human Papillomavirus Infection and Virus Genotyping in Uterine Cervix Cancer in Venezuela
Official title: Observational Study for Determine the Presence and Genotypes of HVP Infection in Cervical Intraepithelial Neoplasia Grade II-III (CIN II-III), and Stage I Cervical Epidermoid Carcinoma and Cervical Adenocarcinoma.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cervical Cancer
Keywords: cervical cancer
Human Papillomavirus Infection
Lead sponsor: Instituto Oncologico Luis Razetti
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2009-07-13
Enrollment: 329
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: cervical samples

Brief summary: 1. Hypothesis:

   If high risk genotypes of human papillomavirus (HPV) is the cause of cervical cancer worldwide, the genotypes associated with cervical cancer in Venezuela would be the same types found in other countries.
2. Objectives:

Primary objective:

The objective of this investigation is to determine the presence and genotypes of HVP infection in cervical intraepithelial neoplasia grade 2/3 (CIN 2/3), and Stage I cervical epidermoid carcinoma and cervical adenocarcinoma.

Specific objectives:

To establish the presence of HPV in cervical cancer patients in Venezuela by geographic distribution.

To establish which HPV types are linked with cervical cancer in Venezuela by geographic distribution.

Detailed description: In Venezuela, cervical cancer is the second leading cause of cancer mortality in women. In developed countries, although it is not the first cause of cancer mortality, occupies a remarkable place in the neoplastic pathology (Cannistra, 1996; Dey, 1998).

Human Papilloma Virus (HPV) is involved in the development of cervical cancer, specially oncogenic types 16 and 18 (Koskela, 2000; Markowska, 1999).

To date, it is still unknown which HPV types are more frequent in Venezuela. Several studies made in this country concluded that HPV 16 is the predominant type in cervical pathology (Graterol 2006, Correnti 1997, Muñoz 2003), but there has not been performed a HVP genotyping to detect all the types involved in patients with cervical cancer. Neither has been establish which HPV types are more frequently involved in genital warts in Venezuela.

The goal of this investigation is perform a genotypification of HPV in cervical cancer and cervical intraepithelial neoplasia 2 and 3 in Venezuela to determine which types are more frequently related to this disease in our country.

4. STUDY DESIGN:

4.1. Collection of cervical samples:

1. Previous ethics committee approval (Instituto Venezolano de Investigaciones Cientificas and Instituto de Oncología Luis Razetti), we are going to collect paraffin blocks of 300 patients with histological diagnosis of CIN 2-3 or Stage I cervical cancer.

The samples will be obtained from archives of the Pathology Units of the following medical centers in Venezuela: Instituto de Oncología Luis Razetti, Anatomía Patológica Universidad Central de Venezuela(Caracas), Hospital Oncológico Pérez Carreño (Valencia), Maracaibo, Barquisimeto, Ciudad Bolívar, Puerto La Cruz, Mérida and Barinas.

Inclusion criteria:

1. Paraffin blocks with CIN 2/3, and Stage I cervical cancer biopsies obtained between 2001 and 2011.
2. Properly blocks identification in order to obtain personal and clinical patient information.

4.2. Molecular biology procedures:

1. Histologically handling of tissue: previous identification of pathologic lesions as described in inclusion criteria by an expert pathologist (sample with lesion but without necrosis), the paraffin block will be cut into 5 to 7 µm slides with new blades and gloves for each cut. It will be obtain 1 slides that will be distributed as follows: one sample will be send to Laboratorio de Virología Molecular del Instituto Venezolano de Investigaciones Científicas; the remained sample will be kept for further evaluation if is necessary. Each slide will be placed in a proper container and will be identified by a serial number in order to preserve patient intimacy and avoid biased results.
2. Deparaffinisation as described in Coombs 1999.
3. Tissue digestion, DNA extraction and precipitation as described in Gravitt 2000.
4. HPV genotyping will be detected by INNOLiPA system. The results will be correlated with clinical information.

Eligibility criteria: Inclusion Criteria:

paraffin blocks of 329 patients with histologic diagnosis of CIN 2, CIN 3 or Stage I cervical cancer. -

Exclusion Criteria:

-

Primary outcomes:
measure: HPV Identification
timeFrame: 6 months
measure: HPV Type 16
timeFrame: 6 months
measure: HPV Type 18
timeFrame: 6 months
measure: HPV Type 31
timeFrame: 6 months
measure: HPV Type 33
timeFrame: 6 months
measure: HPV Type 45
timeFrame: 6 months
measure: HPV Type 58
timeFrame: 6 months
measure: HPV Type 51
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Caracas
country: Venezuela
facility: Instituto Oncologico Luis razetti
state: DF
city: Caracas
country: Venezuela
facility: Jorge Sanchez Lander
state: Miranda
Study officials:
affiliation: Instituto Oncologico Luis Razetti
name: Jorge sanchez, MD
role: PRINCIPAL_INVESTIGATOR
References: