I) Atypical Squamous Cells of Undetermined Significance (ASC-US), II) Atypical Glandular Cells of Uncertain Significance (AGUS), III) Cervical Intraepithelial Neoplasia (CIN), CIN-1, CIN-2, CIN-3, IV) Low-grade Squamous Intraepithelial Lesion (LSIL), V) High-grade Squamous Intraepithelial Lesion (HSIL), VI) Cervical Cancer
Conditions
Keywords
Cervical precursor lesions, LSIL, HSIL, CIN, Reactive cellular changes, Cervical cancer
Brief summary
This study compares how effective is the molecular screening (a blood test) using Pap smear as reference, that is, a comparison of these tests abilities to detect precursor lesions and cervical cancer among women of an open population
Detailed description
The primary goal of this study is to compare the efficacy of liquid-based cytology (Pap smear) with the molecular screening -of three human biomarkers- in their ability to detect reactive cellular changes in the cervix among an open population. Participants will be asked to attend two study visits. All the clinical procedures will be done on the first visit: 1. Explanation of the study and its procedures. Only participants that give their written Informed Consent will be enrolled in the study. 2. Interview and physical examination to obtain a medical record. The interview will collect information related to known risks factors for cervical lesions. 3. Venipuncture to obtain a blood sample. 4. Colposcopy to obtain a cervical smear and a colposcopic diagnosis. The cervical smear will be used to perform liquid-based cytology and HPV detection. 5. Biopsy, only if the gynecologist detects a cervical lesion or another abnormality during colposcopy. The gynecologist will make preliminary recommendations based on the colposcopic findings. During the second visit the study's gynecologist will explain the tests' results and provide clinical recommendations to each participant. The sensitivity, specificity, and predictive values of liquid-based cytology, HPV detection, and molecular screening will be calculated using colposcopy (for all participants) and histopathology (for those biopsied). These results will be compared using a DeLong test. Correlation tests will be performed using risk factors data and test results.
Interventions
PROCEDUREPhysical examination
Physical examination and interview for obtaining a medical record of each participant
Screening test for cervical precursor lesions and/or cancer. LBC is a procedure in which a cervical smear is examined under the microscope
OTHERMolecular screening
The molecular screening detects three human biomarkers associated with cervical precursor lesions and/or cervical cancer. Biomarker detection is done by Western blot and ELISA in human sera
OTHERHPV DNA test
HPV DNA detection is performed using a cervical swab
DIAGNOSTIC_TESTColposcopy
A diagnostic procedure to visually examine the cervix, vagina, and vulva with a colposcope
DIAGNOSTIC_TESTHistopathology
Is the definitive diagnosis of cervical precursor lesions and cervical cancer. It is the microscopic study of diseased cells and tissues stained with hematoxylin and eosin
Sponsors
Timser SAPI de CV
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Given this is a screening study: I) Participant. All enrolled participants will be asymptomatic women. Group assignment will be defined after colposcopy or histopathology (when applicable). II) Care Provider. The gynecologist will not have a priori knowledge of the condition of the participant. During colposcopy only those participants with abnormal results will be biopsied. III) Investigator. None of the investigators performing the tests (cytology, HPV detection, molecular screening, or histopathology) will know each other's results.
Intervention model description
Group 1. All participants will receive a colposcopy, Pap smear, and a venipuncture. Diagnosis by colposcopy will set four clinical groups: negative control (CTR), low-grade squamous intraepithelial lesions LSIL (CIN-1), high-grade squamous intraepithelial lesions HSIL (CIN-2/3), and cervical cancer (CC). Group 2. The participants in groups LSIL, HSIL, and CC will be biopsied. The histopathology analysis of the biopsy is the gold standard for the diagnosis.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Be in good general health. * Age 18-85 years. * A minimum fast of 6 hours and no more than 12 hours. * Refrain from sexual intercourse 24 hours before the study. * Give written informed consent.
Exclusion criteria
* Having a subtotal, total, or radical hysterectomy. * Being pregnant or suspected of being pregnant. A rapid urine test will be performed. If the result is positive, the patient will be excluded from the protocol and referred for prenatal care. * Being under oncological treatment (chemotherapy, radiotherapy and/or brachytherapy). * Being on their period. * Have a previous confirmatory diagnosis of HIV and/or hepatitis infection. * Having taken antiplatelet medications, e.g., acetylsalicylic acid, at least 24 hours before the study. Discontinuation Criteria: * If the participant refuses any of the study procedures. * If the study gynecologist detects that the participant has had a hysterectomy. * If the volume of the biological samples is insufficient for testing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Liquid-based Cytology results (categorical) | Cervical smear will be taken during the first visit (Day 1). LBC results will be available within a maximum of 20 days after sampling. This test will be performed by a Licensed Clinical laboratory. All participants will be subjected to this test. | Cytology's results: Negative to lesion/malignancy. Negative with inflammation. Negative with sexually transmitted infection. Negative with HPV/Herpes cytopathic changes. Negative with atrophy. Positive with ASC-US. Positive with ASC-H. Positive with AGUS. Positive with CIN-1. Positive with CIN-2. Positive with CIN-3. Positive with carcinoma in situ. Positive with LSIL/HSIL. Positive with adenocarcinoma. Positive with Cancer/Malignancy. Positive with probable lesion/cancer/malignancy. |
| Molecular screening result (numeric) | Blood samples will be taken during the first visit (Day 1). Molecular screening results will be available within a maximum of 20 days after sampling. All participants will be subjected to this test | Molecular screening detects three human protein biomarkers in human sera by Western blot and ELISA. Western blot results are qualitative (band intensity units or IU) and ELISA results are quantitative (ng/mL). The final result for molecular screening test is computed as follows: Negative. Only if the three independent biomarkers are below their cutoff values. Positive. If any of the three independent biomarkers is equal to or greater than its cutoff value. Cutoff values will be calculated using a ROC curve with the gold standard. |
| HPV test results (categorical) | Cervical smear will be taken during the first visit (Day 1). HPV test results will be available within a maximum of 20 days after sampling. This test will be performed by a Licensed Clinical laboratory. All participants will be subjected to this test. | HPV test will detect fifteen different high-risk genotypes by PCR: HPV-16 genotype. HPV-18 genotype. HPV-pool (including HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 67, and 68 genotypes). The final test result will be assigned as follows: Positive HPV test: If at least one of the fifteen genotypes is detected on the sample. Negative HPV test: Only if none of the fifteen genotypes are detected on the sample. |
| Colposcopy diagnosis (categorical) | Colposcopy will be performed during the first visit (Day 1). This diagnostic test will be performed by a licensed gynecologist. All participants will be subjected to this diagnostic test. Colposcopy will be used as a reference test. | Colposcopy is the exploration of the female genitalia -vulva, vagina, and cervix- using a lighted magnifying instrument (colposcope). Its accuracy is higher than that of the cytology. If the gynecologist detects/suspects a lesion or malignancy during colposcopy, a biopsy will be drawn for histopathologic analysis. Colposcopy results: Negative with no alterations. Negative with inflammation. Negative with condyloma/condylomatosis/HPV. Negative with atrophy. Negative with squamous metaplasia. Negative with ectropion/ectopy/cervical erosion/cervical eversion/glandular eversion. Negative with Nabothian cysts. Negative with cervical polyp. Negative with Lichen sclerosus. Positive with CIN-1. Positive with CIN-2. Positive with CIN-3. Positive with carcinoma in situ CIN-3. Positive with neoplasia/invasive neoplasia. Positive with LSIL/HSIL. Positive with probable lesion/CIN/LSIL/HSIL. |
| Histopathology diagnosis (cathegorical) | The biopsy for histopathology will be drawn during the first visit (Day 1). Histopathology is the gold standard for cervical cancer diagnosis. Biopsies will be drawn only from women with positive colposcopy results. | Histopathology is the microscopic analysis of a stained slide of a cervical biopsy by a licensed pathologist. The standard staining is H\&E (hematoxylin and eosin). Histopathology results: Negative with normal tissue. Negative with cervicitis. Negative with HPV/Herpes infection. Positive with CIN-1. Positive with CIN-2. Positive with CIN-3. Positive with carcinoma in situ CIN-3. Positive LSIL/HSIL. Positive with microinvasive/invasive cancer. Positive with adenocarcinoma. Positive with sarcoma and other tumors. Positive with carcinoma of unknown primary origin/unspecified malignancy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Age (numeric) | During the first visit (Day 1). | The study physician will record the participants date of birth. Age (in years) will be calculated in reference to the first visit date. |
| Body Mass Index BMI (numeric) | During the first visit (Day 1). | The study physician will record the participants: Weight in kilograms (kg). Height in meters (m). The Body Mass Index will be calculated as follows: BMI = kg/m\^2. |
| Blood pressure (numeric) | During the first visit (Day 1). | Blood pressure is the amount of force the blood uses to get through the circulatory system measured in mmHg. It consists of two measurements: Systolic pressure, e.g., 120 mmHg. Diastolic pressure, e.g., 80 mmHg. The final result will display the two independent measurements, e.g., 120/80 mmHg. |
| Ethnicity (categorical) | During the first visit (Day 1) by clinical interview. | Ethnicity data will be obtained through clinical interview. Ethnicity is linked to cultural expression and identity. Ethnicity options: Hispanic/Latino. Not Hispanic/Latino. |
| Race (categorical) | During the first visit (Day 1) by clinical interview. | Race data will be obtained through clinical interview. Race is linked to physical characteristics. Race options: American Indian. Alaska Native. Asian. Black or African American. African Mexican. Native Hawaiian or Other Pacific Islander. Mexican Original People. White. |
| Age at Menarche (numeric) | During the first visit (Day 1) by clinical interview. | Age at menarche -in years- will be obtained during the clinical interview. Menarche is the first menstrual period in a female adolescent, typically occurs between the ages of 10 and 16. |
| Age at sexual debut (numeric) | During the first visit (Day 1) by clinical interview. | The age at sexual debut -in years- will be obtained during the clinical interview. The age will be recorded in years. |
| Number of years since menarche to sexual debut (numeric) | During the first visit (Day 1) by clinical interview. | The number of years since menarche to sexual debut will be calculated as follows: NYSMSD = Age of Sexual Debut - Age of Menarche. |
| Number of lifetime sexual partners (numeric) | During the first visit (Day 1) by clinical interview. | The number of lifetime sexual partners of the participants will be obtained during the clinical interview. |
| Number of years since last cytology (numeric) | During the first visit (Day 1) by clinical interview. | The year of last or previous cytology will be obtained during the clinical interview. The number of years since las cytology will be calculated as follows: NYSLCy =Year of Participation in the Study - Year of Last/Previous Cytology. |
| Number of years since colposcopy (numeric) | During the first visit (Day 1) by clinical interview. | The year of last or previous colposcopy will be obtained during the clinical interview. The number of years since last colposcopy will be calculated as follows: NYSLCo =Year of Participation in the Study - Year of Last/Previous Colposcopy. |
| Number of abortions (numeric) | During the first visit (Day 1) by clinical interview. | The number of abortions will be obtained during the clinical interview. |
| Number of vaginal deliveries (numeric) | During the first visit (Day 1) by clinical interview. | The number of vaginal deliveries will be obtained during the clinical interview. |
| Number of Caesarean sections (numeric) | During the first visit (Day 1) by clinical interview. | The number of Caesarean sections will be obtained during the clinical interview. |
| Number of cigarettes per week (numeric) | During the first visit (Day 1) by clinical interview. | The number of cigarettes per week will be obtained during the clinical interview. |
Countries
Mexico
Contacts
CONTACTMercedes Gutiérrez-Smith, Bachelor of Arts in History
CONTACTFátima R Ruiz-Rosales, Bachelor of Medicine
PRINCIPAL_INVESTIGATORLeopoldo E Gatica-Galina, MD in OB/GY & Gynecol Oncol
Consultorio Médico TIMSER
Outcome results
None listed