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.

Inclusion Criteria:

- Female

- 18-26 years of age

- Resident of an Appalachian county

- Intact cervix

- Able to read and understand English

- Cognitively able to provide informed consent

- Willing to come for four clinic visits

Exclusion Criteria:

- Prior history of cervical cancer

- Prior history of a cervical lesion treated with cryotherapy or any form of surgical
removal of a portion of the cervix to treat CIN

- No cervix

- Pregnant or planning to become pregnant in the next year

- History of immune disorder: auto-immune, primary immune or acquired

- Any contra-indications for the GARDASIL® vaccine series

- Taking immune suppressive medications

- Any prior exposure to an HPV vaccine of any type

- Planning to move out of the immediate area in the next year