Comparison Of Cytology And Molecular Screening For Detecting Cervical Reactive Cellular Changes In General Population

NCT07211204WithdrawnNAINTERVENTIONAL

Summary

Key Facts

Lead Sponsor

Timser SAPI de CV

Enrollment

0

Start Date

2026-02-27

Completion Date

2026-02-27

Study Type

INTERVENTIONAL

Official Title

Study To Compare The Efficacy Of Cervical Cytology With Molecular Screening In The Detection Of Reactive Cellular Changes In The Cervix In An Open Population

Interventions

Physical examinationLiquid-based cytologyMolecular screeningHPV DNA testColposcopyHistopathology

Conditions

Atypical Squamous Cell of Undetermined SignificanceASC-USAtypical Glandular Cells of Uncertain SignificanceAGUSCervical Intraepithelial Neoplasia (CIN)CIN 1CIN 2CIN 3Cervical Cancer

Eligibility

Age Range

18 Years – 85 Years

Sex

FEMALE

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 (less than 10 mL for the blood sample).

Outcome Measures

Primary Outcomes

Liquid-based Cytology LBC results (categorical)

Study of cells -of the cervix- using a microscope. Cytology is the official screening test for cervical precursor lesions and/or cervical cancer in most countries. 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.

Time frame: 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.

Molecular screening results (dichotomic)

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 are as follows: Biomarker 1 positive \>= 1.37 IU. Biomarker 1 negative \< 1.37 IU. Biomarker 2 positive \>= 17.74 ng/mL. Biomarker 2 negative \< 17.74 ng/mL. Biomarker 3 positive \>= 0.38 IU. Biomarker 3 negative \< 0.38 IU.

Time frame: 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.

HPV test results (categorical)

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. Negative HPV test: Only if none of the fifteen genotypes are detected.

Time frame: 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.

Colposcopy diagnosis (categorical)

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.

Time frame: 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.

Histopathology diagnosis (cathegorical)

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.

Time frame: The biopsy for histopathology will be drawn during the first visit (Day 1). Biopsies will be drawn only from women with positive colposcopy results. Histopathology is the gold standard for cervical cancer diagnosis.

Secondary Outcomes

Body Mass Index (BMI)

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.

Time frame: During the first visit (Day 1).

Blood pressure

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 in mmHg, e.g., 120 mmHg. Diastolic pressure in mmHg, e.g., 80 mmHg. The final result will display the two independent measurements, e.g., 120/80 mmHg.

Time frame: During the first visit (Day 1).

Ethnicity

Ethnicity data will be obtained through clinical interview. Ethnicity is linked to cultural expression and identity. Ethnicity options: Hispanic/Latino. Not Hispanic/Latino.

Time frame: During the first visit (Day 1) by clinical interview.

Race

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.

Time frame: During the first visit (Day 1) by clinical interview.

Age at Menarche

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.

Time frame: During the first visit (Day 1) by clinical interview.

Age at sexual debut

The age at sexual debut -in years- will be obtained during the clinical interview. The age will be recorded in years.

Time frame: During the first visit (Day 1) by clinical interview.

Number of years since menarche to sexual debut

The number of years since menarche to sexual debut will be calculated as follows: NYSMSD = Age of Sexual Debut - Age of Menarche

Time frame: During the first visit (Day 1) by clinical interview.

Number of lifetime sexual partners

The number of lifetime sexual partners of the participants will be obtained during the clinical interview.

Time frame: During the first visit (Day 1) by clinical interview.

Number of years since last cytology

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.

Time frame: During the first visit (Day 1) by clinical interview.

Number of years since colposcopy

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.

Time frame: During the first visit (Day 1) by clinical interview.

Number of abortions

The number of abortions will be obtained during the clinical interview.

Time frame: During the first visit (Day 1) by clinical interview.

Number of vaginal deliveries

The number of vaginal deliveries will be obtained during the clinical interview

Time frame: During the first visit (Day 1) by clinical interview.

Number of Caesarean sections

The number of Caesarean sections will be obtained during the clinical interview.

Time frame: During the first visit (Day 1) by clinical interview.

Number of cigarettes per week

The number of cigarettes per week will be obtained during the clinical interview.

Time frame: During the first visit (Day 1) by clinical interview.

Locations

Clinica Reina Madre Metepec, San Mateo Atenco, Mexico

Linked Papers

2022-12-02

Barriers to uptake of cervical cancer screening services in low-and-middle-income countries: a systematic review

AbstractObjectivesLow-and-middle-income countries (LMICs) bear a disproportionate burden of cervical cancer mortality. We aimed to identify what is currently known about barriers to cervical cancer screening among women in LMICs and propose remedial actions.DesignThis was a systematic review using Medical Subject Headings (MeSH) terms in Google Scholar, PubMed, Scopus, and Web of Science databases. We also contacted medical associations and universities for grey literature and checked reference lists of eligible articles for relevant literature published in English between 2010 and 2020. We summarized the findings using a descriptive narrative based on themes identified as levels of the social ecological model.SettingWe included studies conducted in LMICs published in English between 2010 and 2020.ParticipantsWe included studies that reported on barriers to cervical cancer screening among women 15 years and older, eligible for cervical cancer screening.ResultsSeventy-nine articles met the inclusion criteria. We identified individual, cultural/traditional and religious, societal, health system, and structural barriers to screening. Lack of knowledge and awareness of cervical cancer in general and of screening were the most frequent individual level barriers. Cultural/traditional and religious barriers included prohibition of screening and unsupportive partners and families, while social barriers were largely driven by community misconceptions. Health system barriers included policy and programmatic factors, and structural barriers were related to geography, education and cost. Underlying reasons for these barriers included limited information about cervical cancer and screening as a preventive strategy, poorly resourced health systems that lacked policies or implemented them poorly, generalised limited access to health services, and gender norms that deprioritize the health needs of women.ConclusionA wide range of barriers to screening were identified across most LMICs. Urgent implementation of clear policies supported by health system capacity for implementation, community wide advocacy and information dissemination, strengthening of policies that support women’s health and gender equality, and targeted further research are needed to effectively address the inequitable burden of cervical cancer in LMICs.

2022-11-24

Challenges and opportunities for cervical screening in women over the age of 50 years: a qualitative study

BackgroundCervical cancer is a preventable disease. Cases in women age &gt;50 years are predicted to rise by 60% in the next two decades, yet this group are less likely to attend for screening than younger women.AimTo seek novel solutions to the challenges of cervical screening in women &gt;50 years of age by examining practitioner and service-user experiences.Design and settingSemi-structured interviews were conducted with 28 practitioners and 24 service users &gt;50 years of age, recruited via UK primary care networks in Northern England in 2016–2017, to explore experiences related to cervical screening.MethodAn inductive thematic analysis was conducted to explore the data.ResultsFindings are presented under three key themes. The first,exploring the barriers to successful cervical screening, examines the influences of sexuality and early experiences of screening on attendance, and how preventive health care becomes a low priority as women age. The second,the role of relationships, explores how peer talk shapes attitudes towards cervical screening, how teamwork between practitioners engenders investment in cervical screening, and how interactions between service users and primary care over time can significantly affect intentions to screen. The third,what constitutes good practice, describes practical and sensitive approaches to screening tailored to women aged &gt;50 years.ConclusionGood practice involves attention to structural and practical challenges, and an understanding of the role of relationships in shaping screening intentions. Experienced practitioners adapt procedures to increase sensitivity, and balance time invested in problem solving against the benefits of reaching practice targets for attendance. Building networks of expertise across multiple practices can increase practitioner skill in screening this age group.

2022-06-09

The vaginal microbiome: A complex milieu affecting risk of human papillomavirus persistence and cervical cancer

The purpose of this review is to describe the existing literature regarding the relationship between the vaginal microbiome, human papillomavirus persistence, and cervical cancer risk, as well as to discuss factors that mediate these relationships. Data suggest that alterations in the vaginal microbiome affect the risk of human papillomavirus infection and persistence, which has downstream effects on cervical dysplasia and cancer risk. The homeostatic Lactobillus species L. crispatus, L. gasseri, L. jensenii act to promote a healthy vaginal environment, while L. iners and pathogens causing bacterial vaginosis are associated with increased inflammation, human papillomavirus infection, cervical dysplasia, and potentially cancer. There are, however, still several large gaps in the literature, particularly related to the modifiable and non-modifiable factors that affect the vaginal microbiome and ensuing risk of pre-cancerous and cancerous lesions. Evidence currently suggests that endogenous and exogenous hormones, tobacco products, and sexual practices influence vaginal microbiome composition, but the nuances of these relationships and how changes in these factors affect dysplasia risk are yet to be delineated. Other studies examining how diet, exercise, race, socioeconomic status, and genetic factors influence the vaginal microbiome are difficult to interpret in the setting of multiple confounders. Future studies should focus on how changes in these modulatory factors might promote a healthy vaginal microbiome to prevent or treat dysplasia in the lower female genital tract.

2021-10-05

Barriers and strategies for cervical cancer screening: What do female university students know and want?

Objective This study aimed to identify the distinct barriers and knowledge level of cervical cancer screening among female university students and establish intervention strategies to overcome these barriers. Methods This study used a mixed-methods design with 26 female university students aged 20–29 years. We first conducted a quantitative online survey for the same study participants, divided them into three groups, and conducted focus group interviews (FGIs). Group A: participants who had sexual experience and had undergone cervical cancer screening; Group B: participants who had sexual experience and had not undergone cervical cancer screening; Group C: participants who did not have sexual experience and had not undergone cervical cancer screening. Results The participants’ ages were 21.92 ± 1.26 years. The knowledge levels for cervical cancer and screening were low to moderate. The four main themes that emerged as barriers to cervical cancer screening through the FGIs were: 1) socio-cultural barrier: conservative social perception of unmarried women’s sexual life, 2) knowledge barrier: lack of knowledge and information, 3) psychological barrier: discomfort, and 4) practical barrier: time-consuming. The three themes identified for strategies were: 1) socio-cultural intervention: changing social perceptions and ensuring confidentiality, 2) educational intervention: improvement of knowledge and accessibility, and 3) alternative screening intervention: comfortable screening methods. Conclusions While university students’ sexual experience rapidly increased, the socio-cultural perceptions of sexual health remained closed, and they had a reasonably low level of knowledge about cervical cancer screening. Therefore, various strategies sensitive to female university students’ culture should be implemented to increase the knowledge level, and social efforts should be made to change the socio-cultural perception of unmarried young women’s sexual health.

2020-07-06

Molecular and pathological basis of HPV‐negative cervical adenocarcinoma seen in a global study

AbstractInternational surveys find HPV‐negativity in up to 30% of cervical adenocarcinomas. We investigated the pathological diagnosis by expert consensus with immunohistochemistry and the presence of somatic mutations in recognised tumour genes in HPV‐positive and negative cervical adenocarcinomas (CADC). A sample was selected of 45 paraffin‐embedded cervical blocks diagnosed locally as usual cervical adenocarcinoma from a global study. These represented different diagnoses made at previous diagnostic review and HPV status. All were suitable for analysis for somatic tumour associated gene mutations. Three pathologists examined H/E slides and immunohistochemistry for p16, progesterone receptor and p53 and classified the cases. L1 genes from high‐risk HPVs and low‐risk HPVs were analysed by SPF10 PCR‐DEIA‐LiPA25 version 1 in whole tissue sections and microdissected tumour and retested by PCR for E6/E7 genes of hrHPVs if negative. Cases were analysed for microsatellite instability and next‐generation sequencing mutation analysis. From the 45 cases, 20 cases of usual CADC were confirmed of which 17 (85%) were HPV‐positive in tumour cells. The other 25 cases were reclassified as endometrial, serous, clear‐cell and gastric‐type adenocarcinomas and all were HPV‐negative in tumour cells. Careful retesting for HPV DNA and IHC leads to more accurate identification of HPV‐positive usual cervical adenocarcinomas. Endometrioid endometrial adenocarcinomas, other uterine adenocarcinoma with multiple somatic mutations were important in misclassification of HPV‐negative cases locally managed as cervical adenocarcinoma, as was gastric‐type adenocarcinoma with germline STK11 mutation in East Asia. Few consensuses confirmed HPV‐negative usual cervical adenocarcinomas showed somatic tumorigenic mutations also seen in some HPV‐positive usual CADC.

High parity is associated with increased risk of cervical cancer: Systematic review and meta-analysis of case–control studies

Background: Cervical cancer is the fourth most common cancer among women. High parity has long been suspected with an increased risk of cervical cancer. Evidence from the existing epidemiological studies regarding the association between parity and cervical cancer is variable and inconsistent. Therefore, the objective of this systematic review and meta-analysis was to synthesize the best available evidence on the epidemiological association between parity and cervical cancer. Methods: Case–control studies reporting the association between parity and cervical cancer were systematically searched in databases like MEDLINE/PubMed, HINARI, Google scholar, Science direct, and Cochrane Libraries. All studies fulfilling the inclusion criteria and published between 2000 and 7 March 2020 were included in this meta-analysis. This study reported according to PRISMA guideline. Cochran’s Q-statistics and I 2 tests were performed to assess heterogeneity among included studies. Egger’s regression analysis was performed to assess publication bias. A random-effect meta-analysis model was used to compute pooled odds ratio of the association between parity and cervical cancer. Results: A total of 6685 participants (3227 patients and 3458 controls) were incorporated in the 12 studies included in this meta-analysis. The meta-analysis revealed that women with high parity had 2.65 times higher odds of developing cervical cancer compared to their counterparts (odds ratio = 2.65, 95% confidence interval = 2.08–3.38). Conclusion: High parity is positively associated with cervical cancer. Strong epidemiological studies are recommended to further explore the mechanisms and role of parity in the causation of cervical cancer.