Community Awareness, Resources and Education (CARE II): Project 3
Condition: Uterine Cervical Cancer
MeSH terms: Uterine Cervical Neoplasms
Study type: Observational

Summary: 
      Researchers at The Ohio State University and the University of Michigan are working together
      to understand cancer of the cervix. One of the areas they are studying is how stress you may
      experience in your life effects the way you respond to GARDASIL®. GARDASIL® is a vaccine
      approved by the Food and Drug Administration (FDA) to prevent some types of Human
      Papillomavirus (HPV) infection which can cause cancer of the cervix. Participants are being
      recruited from the Appalachian region of Ohio.
    

Detailed description: 
      A quadrivalent HPV 6, 11, 16, 18 vaccine (GARDASIL®) has been approved for use among women
      age 9-26 years to prevent cervical/vaginal/vulvar cancer and genital warts. The efficacy of
      the vaccine has been demonstrated in clinical trial settings, but the effectiveness of this
      vaccine has not been tested in clinical practice settings. Patients experiencing greater
      stress have a reduced capacity to mount an immune response to other types of vaccine. The
      same phenomenon is likely to exist for Gardasil, but there are no data. The impact of
      psychological stress on the immune response to a vaccine is proposed to act via health
      behaviors (multiple lifetime sexual partners, never using condoms, prior abnormal Pap smear,
      smoking, and HPV infection) or by direct dysregulation of the immune system. We have found
      higher rates of cervical HPV in Appalachian Ohio women, higher rates of abnormal cervical
      cytology, and very high rates of psychological stress compared to urban and suburban women.
      The goal of this study is to determine if, in women age 18-26 years given GARDASIL® vaccine,
      serum HPV 6/11/16/18 antibody response is altered by stress. This will be accomplished by a
      study of 432 women age 18-26 years who report full range of life stressors recruited from
      Appalachian Ohio. All participants will receive the GARDASIL® vaccine at baseline, two
      months, and six months. Prior to vaccination questionnaire data related to HPV exposure risk
      behaviors and psychological stressors will be collected. Cervical samples will be collected
      for cytology and HPV testing. Serum samples will be collected for HPV 6, 11, 16 and 18
      antibody assays at baseline and month 12. The questionnaire data and serum samples will be
      repeated at 12 months. The primary outcome measure is the difference in serum antibodies to
      HPV 6, 11, 16 and 18 at baseline and month 12. The variables of interest are perceived
      stress, sexual behaviors, socioeconomic status, access to health care (health insurance
      yes/no), smoking, Appalachian self-identity, HPV cervical status at baseline, and past
      history abnormal cervical cytology, as proposed in a psychoneuroimmunology model. In this
      model, Appalachian Self-Identity, socioeconomic status, loneliness, health care access, and
      coping are proposed to contribute to a woman's perceived stress. The impact of perceived
      stress on immune response to Gardasil vaccination can be by health behaviors such as multiple
      lifetime sexual partners (>4), never using condoms, prior abnormal Pap smear, smoking, and
      HPV status at the time of vaccination. Perceived stress can have a direct physiologic impact
      on the immune response by creating immune dysregulation as measured by increased EBV VCA-IgG
      titers. Depressive symptoms can mediate the impact of perceived stress on immune function. If
      psychological stress is found to modulate the immune response to GARDASIL®, then we can
      determine if the modulation reduces the clinical effectiveness of the vaccine and examine
      methods to limit the impact of stress.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Participants will be female, aged 18 - 26 years, residing in an Appalachian region, with no
        history of HPV vaccination.
      
Biospecimen description: 
      serum, Pap specimen, cervical specimen for HPV analysis, oral rinse specimen, saliva specimen
    
Keywords: Human Papilloma Virus; vaccine; stress; cervical cancer; GARDASIL