Cervical Cancer Early Endpoints and Determinants
Condition: Cervical Cancer; Cervical Intraepithelial; Neoplasia; CIN
MeSH terms: Uterine Cervical Neoplasms
Study type: Observational

Summary: 
      This study, conducted by the National Cancer Institute and the University of Oklahoma, will
      look for changes in cervix cells and other samples that may be signs of cervical disease.
      Human papilloma virus, or HPV, is a common infection of the genitalia in women that usually
      goes away by itself. If HPV infection does not go away, it might turn into cancer of the
      cervix, although this is rare. This study will examine why many HPV infections go away and
      why a few persist and lead to cervical cancer.

      Women 18 years of age and older who are referred for colposcopy (examination of the vagina
      and cervix using an instrument with a magnifying lens) at the University of Oklahoma
      following Pap smear diagnosis may be eligible for this study. Women will be in one of the
      following diagnostic categories:

        -  Cancer: Stage 1-2 only.

        -  Precancer: Cervical intraepithelial neoplasia (CIN3).

        -  HPV-infected: Positive for any of the 13 known cancer-causing HPV types, but not
           diagnosed with cancer or CIN3.

        -  Normal: Negative for cancer-causing HPV and normal tissue laboratory results.

      Participants will undergo the following procedures:

        -  Questionnaire: Covers demographic information (such as age, race, ethnicity, marital
           status, etc.), pregnancy history, menstrual and sexual history, contraceptive history,
           hormone medication history, medical history, smoking history, physical development,
           family history, and health care access.

        -  Blood test: 2 tablespoons of blood drawn.

        -  Colposcopy.

        -  Procedure to collect a sample of cervical cells and fluids for HPV testing and research.
    

Detailed description: 
      For the past twenty years, large epidemiologic natural history studies have played a crucial
      role in achieving our current understanding of cervical neoplasia. We now know that human
      papillomavirus (HPV) infection is necessary but not sufficient cause of cervical cancer.
      Cervical pathogenesis evolves as follows: normal 'yields' oncogenic HPV infection 'yields'
      precancer 'yields' invasive cancer. The majority of women with oncogenic HPV infections will
      not develop cancer, and most HPV infections, even those with associated cellular changes,
      regress in 1-2 years, probably eradicated or controlled by cellular immune response.
      Morevoer, while invasive cancer and precancer are histologically welldefined, the
      histological classification of low-grade lesions, now better defined as HPV infection, is
      very heterogeneous and poorly reproducible. Identifying women at highest risk for cancer
      prior to neoplastic progression is therefore a challenge. At present, we are unable to
      predict with any accuracy which HPV infections will progress and which are among the majority
      that regress. Currently, cytologic, histologic, and to some extent, HPV DNA assays are the
      basis for triage, treatment, and follow-up. While this approach has permitted successful
      cervical cancer prevention efforts, millions of women are diagnosed each year with HPV
      infections, and because of the inability to distinguish those who will progress from those
      who will regress, many women are over-treated as a result. It is therefore of etiologic
      interest and of public health benefit to develop a method for identifying the HPV-infected
      women at risk for progressing to precancer and invasion. To develop an accurate and
      reproducible division of precursor lesions (HPV infection and precancer) will require gaining
      knowledge about the molecular distinctions at each progressive disease state. Our goal is to
      therefore comprehensively assess biomarkers of risk for progressive cervical neoplasia, and
      thus develop a new set of biomarkers that can distinguish those at highest risk of cervical
      cancer from those with benign infection. Specifically, we will initially implement a
      cross-sectional study to develop a comprehensive list of potential risk biomarkers by
      examining cervical tissues of women with normal, HPV infection, precancer, and cancer. They
      will measure gene expression profiles to gain an accurate and comprehensive in vivo picture
      of cervical neoplasia carcinogenesis. We propose to then validate the most promising
      identified candidate biomarkers in a prospective design by assessing their predictive values
      for key outcomes related to progression (HPV persistence, diagnosis of precancer) or
      non-progression (HPV clearance).
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        The study enrolled women attending the University of Oklahoma Colposcopy Clinic.
      
Keywords: Molecular Markers; Human Papillomavirus; Cervix; Cancer; Microarray