Brief Title
Improving Cervical Cancer Screening Among HIV-Infected Women in India
Official Title
Improving Cervical Cancer Prevention Among HIV-Infected Women Using Novel HPV Based Biomarker Assays
Brief Summary
Background:
- Cervical cancer is a major cause of cancer deaths among women. Most cases of cervical
cancer are caused by the human papillomavirus (HPV). HPV is more common in women who
have the human immunodeficiency virus (HIV). India has one of the highest rates of women
who have both cervical cancer and HIV infection.
- Cervical cancer can be discovered in early stages by screening for HPV infection.
Researchers want to compare new cervical cancer screening tests for HIV-infected women.
They also want to know more about how HPV can lead to cervical cancer in HIV-infected
women. To do so, they will hold a study to screen HIV-infected women in India.
Objectives:
- To improve cervical cancer screening methods in HIV-infected women in India.
Eligibility:
- Women at least 18 years of age who have HIV infection.
- Participants will be recruited from HIV-focused health care clinics in Pune and Chennai,
India.
Design:
- Participants will have a physical exam and medical history. They will provide a urine
sample and proof of HIV infection.
- Participants will have a gynecological exam. This will involve a pelvic exam and Pap
smear to collect cells for study. It will also involve a cervical exam to look for
precancerous cells. Cervical tissue may be collected.
- Participants will also provide a blood sample for testing.
- Participants will return in 2 weeks for the test results. If there are signs of
precancerous or cancer cells, participants will be referred to a doctor for treatment.
Detailed Description
Background:
While HPV DNA testing is a highly sensitive screening method for cervical cancer, it cannot
differentiate between the majority of benign infections and few persistent infections linked
to cervical precancer. Given the high prevalence of carcinogenic HPV DNA and higher risk for
cervical precancer and cancer among HIV-infected women, there is a substantial need for
screening tests that are both adequately sensitive as well as specific, so as to maximize
detection while reducing false-positive referrals. Furthermore, the unique immunological
milieu in HIV-infected women presents significant opportunities to study natural history of
HPV-mediated cervical oncogenic process in the context of immunosuppression.
Objectives and Methods:
The primary objective is to evaluate the clinical performance of two novel biomarker assays
for detection of histologically-confirmed cervical intraepithelial neoplasia grade 2/3 or
more severe (greater than or equal to CIN2 and greater than or equal to CIN3) among
HIV-infected women. These tests include: (i) immunocytostaining by p16(INK4a)/Ki-67
(biomarkers correlated with the oncogenic transformation of cervical cells following
persistent carcinogenic HPV infection) and (ii) testing for HPV E6/E7 mRNA (expressed during
progression of a transient to a transforming HPV infection). Secondary objectives include
studying the association of risk factors and biomarkers with specific HPV genotypes and
studying the interaction of HIV and HPV in cervical disease categories and in the context of
immunosuppression.
Eligibility:
HIV-infected women, 18 years or older, with no history of previous treatment for cervical
precancer/cancer, not currently pregnant, and able to provide informed consent.
Design:
This cross sectional study will be conducted in collaboration with Indian Council of Medical
Research (ICMR), in three institutions, with substantial experience in conduct of clinical
research on HIV/AIDS and HPV/cervical cancer: the National AIDS Research Institute (NARI) in
Pune, the National Institute of Epidemiology (NIE) in Chennai, and the Jawaharlal Nehru
Medical College (JNMC) in Belgaum. A total of 1000 HIV-infected women attending HIV care and
treatment clinics in Pune (n=400) and Chennai (n=400), and Belgaum (n=200) will be recruited.
According to routine practice, participants will undergo per-speculum examination and
cervical specimen collection, followed by a detailed diagnostic colposcopy exam with biopsies
as indicated for histological analysis. Cervical specimens will be used for liquid-based
cytology as well as simultaneous independent assessment with p16(INK4a)/Ki-67 and HPV E6/E7
mRNA testing. HPV DNA genotyping will be conducted by Linear Array HPV polymerase chain
reaction. We will estimate the clinical performance (sensitivity, specificity, positive and
negative predictive values, Youden s Index, and positive and negative likelihood ratios with
95% confidence intervals) of individual tests and combinations for prevalent detection of
histologically-confirmed greater than or equal to CIN2 and greater than or equal to CIN3
among HIV-infected women. Additionally we will estimate age-specific and disease-specific HPV
prevalence rates and HPV genotype composition, examine factors associated with greater than
or equal to CIN2/greater than or equal to CIN3 lesions, examine the relationships of
biomarker positivity at the HPV genotype-specific level, and evaluate the role of
immunosuppression on HPV-mediated carcinogenesis. This study will permit validation of
collection, transport, storage, and implementation protocols, allow evaluation of the field
adoption and efficacy of these newer assays, describe the sensitivity and specificity of any
of the tests or combinations with reasonable precision for a wide range of prevalence of
greater than or equal to CIN3, and provide a resource for studies of HIV-HPV coinfection.
Study Type
Observational
Primary Outcome
Cervical Intraepithelial Neoplasia Grade II or more severe
Condition
Cervical Cancer
Study Arms / Comparison Groups
Cohort
Description: HIV-infected women attending HIV care and treatment clinics in Pune, Chennai, andBelgaum in India.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
1000
Start Date
November 28, 2012
Completion Date
October 8, 2020
Primary Completion Date
October 8, 2020
Eligibility Criteria
- INCLUSION CRITERIA:
1. Female greater than or equal to 18 years of age at study entry. This ensures that
all participants are at or above legal age in India for giving informed consent.
2. Confirmed HIV-1 infection.
3. For women of reproductive potential, a negative urine pregnancy test with a
sensitivity of <25mlU/mL prior to study entry. This ensures that only
non-pregnant women are included. While pregnancy is not an absolute
contraindication for screening, certain invasive clinical procedures are often
postponed until after pregnancy.
4. If recently given birth, must be at least 12 weeks postpartum.
5. Physical and mental ability and willingness of participant to provide written
informed consent.
EXCLUSION CRITERIA:
1. Current or prior history of cervical, vaginal, or vulvar cancer.
2. Prior treatment for cervical disease; including treatment by cervical cryotherapy,
LEEP, cervical conization, total or partial hysterectomy, chemotherapy, or radiation
therapy.
3. Prior cervical procedure in the past 6 months, including dilatation and curettage
(D&C).
4. Serious illness requiring systemic treatment or hospitalization within 21 days prior
to study entry.
5. Active drug or alcohol use or dependence or any other condition that, in the opinion
of the site investigator, would interfere with the participant s ability to adhere to
study requirements.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Nicolas Wentzensen, M.D., ,
Location Countries
India
Location Countries
India
Administrative Informations
NCT ID
NCT02247999
Organization ID
999913037
Secondary IDs
13-C-N037
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Nicolas Wentzensen, M.D., Principal Investigator, National Cancer Institute (NCI)
Verification Date
October 2020