Trial Information

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.

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.