Trial Information

Community Awareness, Resources and Education (CARE II): Project 3

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.