The Johns Hopkins Medical
Institutions, located in inner city Baltimore, serve the medical needs
of a multi-racial population including many individuals from the
immediate neighborhood and from a tri-state region. The clinical
patient care and service resources available at Johns Hopkins will be
well integrated with the research activities of the SPORE. Patients
will be recruited from the Johns Hopkins Colposcopy Service, from the
Kelly Gynecologic Oncology Service, and from referring physicians.
Annually, the Colposcopy Service treats over 800 patients, approximately
15% of whom have high-grade lesions, about 2/3 of which are CIN3. Of
these, approximately 60% are caused by HPV16. Approximately 33% of
these patients are African-American. In the JHH Moore Clinic, which
serves HIV-seropositive patients, approximately 6 colposcopies per month
are performed. The rate of high-grade preinvasive disease is
approximately 20%. Of these patients, 90% are African American. It is
estimated that approximately 75% of those approached to screen for study
entry would be willing to participate. In 2001, the Johns Hopkins
Hospital Kelly Gynecologic Oncology Service volume indicates a total of
101 new cases of cervical cancer and 23 recurrent cervical cancers; 62%
of these women were white, 33% of them were African-American, and 5% of
them were of other ethnic backgrounds. The patient population for the
research studies is representative of the patient population of The
Johns Hopkins Hospital catchment area. Women who received part or all
of their therapy at Johns Hopkins show the following approximate stage
distribution: 52% Stage I, 22% Stage II, 18% Stage III, and 8% Stage
IV. Furthermore, this SPORE will recruit patients for trials from other
hospital centers including The Johns Hopkins Bayview Medical Center, The
Johns Hopkins Outpatient Center at Greenspring (a satellite clinic), and
the Greater Baltimore Medical Center (GBMC).
It is recognized that
optimal accrual to this study may require a larger referral population
than that within the Johns Hopkins institutions. SPORE investigators
such as Drs. Deborah Armstrong and Fredrick Montz have strong working
relationships with most of the gynecologic oncologists within a fairly
large geographic radius. These gynecologic oncologists frequently refer
patients for second opinions for systemic, non-surgical therapies or for
unique treatment options that are not available in the community. This
resource will be fully utilized so that the largest possible population
of eligible women with cervical cancer will be available for
consideration of treatment on this trial. It is expected that this will
provide a sufficient population base for the projected rate of accrual
to this study. However, if study accrual is insufficient, consideration
will be given to utilizing the Gynecologic Oncology Group (GOG) as a
resource. Investigators on this SPORE have a strong working
relationship with the GOG, serving on the vaccine subcommittee (Drs.
Trimble and Pardoll), developmental therapeutics committee (Dr.
Armstrong) and phase I subcommittee (Dr. Armstrong).
In addition, the University
of Michigan School of Medicine in Ann Arbor, Michigan, operates an
NCI-designated Comprehensive Cancer Center that routinely evaluates and
treats patients with HPV-associated SIL and carcinoma. Located
approximately 40 miles from Detroit, Michigan, it is positioned to serve
a sizable cervical cancer patient population. For Project 2, the
University of Michigan and its associated clinics will also provide an
adequate patient base and amount of patient specimens. Project 3 will
include seroepidemiological studies not only of women from Costa Rica
(see below), but also women enrolled in the HERS and WIHS, two large
cohort studies of HIV-seropositive women and risk-matched HIV-seronegative
women. Thus, a large population of women at risk for or with
established cervical cancer will be eligible for participation in
research trials in the SPORE program.
In industrialized societies
where Pap smear screening was introduced in the 1950s, a substantial
reduction of cervical cancer incidence was achieved. However, for a
variety of reasons, effective Pap smear programs have not been
established and maintained in areas of high cervical cancer incidence
such as India, Latin America and Africa. To address this issue, we have
included two projects (Projects 1 and 3) that focus on geographic areas
with a high prevalence of cervical cancer (India and Costa Rica). For
example, in India, cervical cancer is the most common female malignancy
with an annual incidence of 30 cases per 100,000 women and kills 61,000
women annually (Gopalan, Voluntary Health Association of India,1999).
In Costa Rica, the prevalence of cervical cancer is approximately 25 per
100,000 (Parkin, International Association of Cancer Registries,1992),
and is even higher in the province of Guanacaste (Schiffman, JAMA,
2000). Project 1 includes patients from Medchal Mandal, a rural
community in India with a substantial population of potential patients,
approximately 12,000 women age 30 and older served by the MediCiti
Hospital and community clinics. Thus, patient populations such as those
in Guanacaste, Costa Rica (Project 3) and Medchal Mandal, India (Project
1) are a key focus of the SPORE. By enrolling, examining, and treating
patients in these high-risk areas, the SPORE will have access to
patients in regions where screening, diagnosis, and treatment for
cervical cancer are not readily available, and allow the acquisition of
samples to gain valuable insight into the biology, immunology, and
carcinogenesis of HPV.
Gathering of patient
resources in the SPORE will be carefully coordinated by the
Tissue/Pathology Core. Patient information and data will be analyzed
and integrated under the guidance of the Biostatistics/Bioinformatics
Core. Both activities will be overseen by the
Administration/Communication Core and the Clinical Research Director and
Clinical Research Coordinator. Patient data will be shared and
safeguarded in a secure database and made available via a virtual
private network accessible only to authorized SPORE investigators.
The combined patient base
served by the Johns Hopkins University, the University of Michigan, and
affiliated clinics in Guanacaste, Costa Rica and Medchal, Mandal, India
will provide a sizable volume of patient material and allow for
organization and analysis of valuable patient data, which will serve the
needs of the SPORE as outlined in the individual programs.
In addition to the
geographic resources afforded by enrollment of patients in Costa Rica
and India, specific efforts are being made to recruit minorities for
clinical trials including African Americans and Hispanics by selection
of appropriate community organizations. The population of subjects
enrolled in all the projects will have an excellent representation of
minority women. There will be no policy or effort to limit or exclude
study subjects from any ethnic group.
