Cervical CancerNCT02247999
Improving Cervical Cancer Screening Among HIV-Infected Women in India
An observational study of Cervical Cancer and HIV/AIDS, run by National Cancer Institute (NCI) at 1 site in India.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cervical Cancer, HIV/AIDS, HPV
- How many people
- 1,000 participants
- Where
- 1 siteIndia
- Study dates
- 28 Nov 2012to 8 Oct 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: The study population will be selected from HIV-infected women attending HIV care and treatment clinics in Pune, Chennai, and Belgaum in India.
Who may be able to join
- 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.
- Confirmed HIV-1 infection.
- 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.
- If recently given birth, must be at least 12 weeks postpartum.
- Physical and mental ability and willingness of participant to provide written informed consent.
Who cannot join
- Current or prior history of cervical, vaginal, or vulvar cancer.
- Prior treatment for cervical disease; including treatment by cervical cryotherapy, LEEP, cervical conization, total or partial hysterectomy, chemotherapy, or radiation therapy.
- Prior cervical procedure in the past 6 months, including dilatation and curettage (D\&C).
- Serious illness requiring systemic treatment or hospitalization within 21 days prior to study entry.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Improving Cervical Cancer Prevention Among HIV-Infected Women Using Novel HPV Based Biomarker Assays
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.
Read more
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.
Read the 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.
- Conditions
- Cervical Cancer, HIV/AIDS, HPV, Cervical Intraepithelial Neoplasia, Biomarkers
- Keywords
- Cervical Cancer, HIV/AIDS, HPV, Biomarkers, Screening
- Medical subject headings
- Uterine Cervical Neoplasms, Acquired Immunodeficiency Syndrome, Uterine Cervical Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cohort | HIV-infected women attending HIV care and treatment clinics in Pune, Chennai, andBelgaum in India. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cervical Intraepithelial Neoplasia Grade II or more severe
Cervical Intraepithelial Neoplasia Grade II or more severe
Measured: At enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2014 (estimated)
- Study start28 Nov 2012
- Primary completion8 Oct 2020
- Study completion8 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cervical CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 1,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Nicolas Wentzensen, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02247999
- Sponsor's protocol ID
- 999913037
- Other IDs
- 13-C-N037
- Status last verified
- Oct 2020
- First submitted
- 20 Sep 2014
- Last updated
- 9 Oct 2020
- Results posted
- No
Publications
Sahasrabuddhe VV, Luhn P, Wentzensen N. Human papillomavirus and cervical cancer: biomarkers for improved prevention efforts. Future Microbiol. 2011 Sep;6(9):1083-98. doi: 10.2217/fmb.11.87.
PubMed 21958146Wentzensen N, Fetterman B, Castle PE, Schiffman M, Wood SN, Stiemerling E, Tokugawa D, Bodelon C, Poitras N, Lorey T, Kinney W. p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in HPV-Positive Women. J Natl Cancer Inst. 2015 Sep 15;107(12):djv257. doi: 10.1093/jnci/djv257. Print 2015 Dec.
PubMed 26376685Mane A, Nirmalkar A, Risbud AR, Vermund SH, Mehendale SM, Sahasrabuddhe VV. HPV genotype distribution in cervical intraepithelial neoplasia among HIV-infected women in Pune, India. PLoS One. 2012;7(6):e38731. doi: 10.1371/journal.pone.0038731. Epub 2012 Jun 19.
PubMed 22723879
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Cervical Cancer Prevention Among HIV-Infected Women Using Novel HPV Based Biomarker Assays
- ClinicalTrials.gov ID
- NCT02247999
- Acronym / sponsor ID
- 999913037
- Conditions
- Cervical Cancer, HIV/AIDS, HPV, Cervical Intraepithelial Neoplasia, Biomarkers
- Keywords
- Cervical Cancer, HIV/AIDS, HPV, Biomarkers, Screening
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,000 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 28 Nov 2012 (actual)
- Primary completion
- 8 Oct 2020 (actual)
- Study completion
- 8 Oct 2020 (actual)
- First posted
- 25 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cohort | – | –HIV-infected women attending HIV care and treatment clinics in Pune, Chennai, andBelgaum in India. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population will be selected from HIV-infected women attending HIV care and treatment clinics in Pune, Chennai, and Belgaum in India.
Key inclusion criteria (5 listed)
Key exclusion criteria (5 listed)
- Current or prior history of cervical, vaginal, or vulvar cancer.
- Prior treatment for cervical disease; including treatment by cervical cryotherapy, LEEP, cervical conization, total or partial hysterectomy, chemotherapy, or radiation therapy.
- Prior cervical procedure in the past 6 months, including dilatation and curettage (D\&C).
- Serious illness requiring systemic treatment or hospitalization within 21 days prior to study entry.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Cervical Intraepithelial Neoplasia Grade II or more severe
Time frame: At enrollment
Cervical Intraepithelial Neoplasia Grade II or more severe
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2020.
- Background: PubMed 21958146Sahasrabuddhe VV, Luhn P, Wentzensen N. Human papillomavirus and cervical cancer: biomarkers for improved prevention efforts. Future Microbiol. 2011 Sep;6(9):1083-98. doi: 10.2217/fmb.11.87.
- Background: PubMed 26376685Wentzensen N, Fetterman B, Castle PE, Schiffman M, Wood SN, Stiemerling E, Tokugawa D, Bodelon C, Poitras N, Lorey T, Kinney W. p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in HPV-Positive Women. J Natl Cancer Inst. 2015 Sep 15;107(12):djv257. doi: 10.1093/jnci/djv257. Print 2015 Dec.
- Background: PubMed 22723879Mane A, Nirmalkar A, Risbud AR, Vermund SH, Mehendale SM, Sahasrabuddhe VV. HPV genotype distribution in cervical intraepithelial neoplasia among HIV-infected women in Pune, India. PLoS One. 2012;7(6):e38731. doi: 10.1371/journal.pone.0038731. Epub 2012 Jun 19.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolas Wentzensen, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cervical Cancer and HIV/AIDS, run by National Cancer Institute (NCI) at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cervical Intraepithelial Neoplasia Grade II or more severe (time frame: At enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02247999, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2020.