Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Immune System Diseases

Uterine Cervical Neoplasms

Hypersensitivity

Precancerous Conditions

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

A random sample of HPV positive women with negative cytology will be invited to repeat HPV DNA test and biomarkers after a year, as recommended by the current screening protocols based on HPV DNA

Experimental: immediate colposcopy. A random sample of HPV positive women with negative cytology will be sent to immediate colposcopy

A immediate colposcopy in this arm may detect potentially spontaneous regressive cervical lesions, so may determine an over diagnosis and over treatment, which the study want to estimate

Experimental: immediate colposcopy

Enza Di Felice

Antonio Ferro

Francesca Carozzi

Massimo Confortini

Vincenzo Maccallini

Basilio Passamonti

Luisa Paterlini

Maria Concetta Tufi

Paolo Dalla Palma

Guglielmo Ronco

Paolo Giorgi Rossi, PhD

In industrialized countries, cervical cancer is a well controlled disease thanks to the diffusion of Pap test and, in particular, to organized screening programs, which are able to detect and treat pre-invasive lesions (cervical intraepithelial neoplasia, CIN). The human papilloma virus (HPV) has been recognised as the necessary, but not sufficient, cause of cervical cancer, so a new screening test based on the identification of high risk (HR) HPV types has been developed(HPV DNA test). This test has demonstrated to be more effective than cytology in reducing the incidence and the mortality of cervical cancer, but it is less specific, so the use of a test triage is necessary to reduce the number of colposcopies and the risk of over-diagnosis (due to the potential regressivity of pre-invasive lesions). Until now, the triage test used is the cytology (Pap test).

Recently specific biomarkers (mRNA and p16 tests) have been introduced for high grade CIN, targeting the molecular alterations strictly associated to transformation rather than simply detecting HR-HPV infections. These tests are more specific than HPV DNA test with a modest reduction of sensitivity for high-grade lesions.

This is a multicenter randomised trial nested into some Italian screening programs based on the use of HPV DNA test as primary test.

All women with positive HPV DNA test will be tested for cytology and also for mRNA and p16. Women with positive cytology will be referred to colposcopy, while women with negative cytology will be randomized into two arms.

This study aims to evaluate if mRNA and p16 could be used as test of triage of HPV DNA or as a primary screening test with direct sending in colposcopy.

In particular the main objectives are:

* Measuring the cumulative detection rate of CIN2+ in the five years following a HPV DNA positive test and mRNA or p16 negative.
* Measuring the potential reduction of overdiagnosis of using mRNA or p16 test instead of DNA, with direct sending in colposcopy
* Measuring the reduction of overdiagnosis of cytological triage or triage with mRNA or p16 compared to the direct sending in colposcopy in women with HPV DNA test positive.

Secondary objectives are:

* to assess the feasibility of mRNA testing in primary screening
* to validate the sample techniques for the new tests
* to standardize quality controls for the the new tests

Individual data about the following study steps are collected according a fixed format:

1. recruited women
2. HPV DNA result
3. cytology and randomization results
4. p16 result
5. mRNA result
6. colposcopies (with relative cytology and histologies) results
7. Women excluded after informed consent
8. Interventions During the first year of recruitment, there will be two semi-annual sending of data, then each year.

To analyze the study progress in each center, summary tables will periodically send to the PI.

All CIN lesions and cancers found in the study will be be blindly reviewed. A set of quality assurance procedures will be implemented for both the molecular tests, including the use of controls provided by the manufacturers with known HPV DNA or mRNA content and the circulation of clinical samples prepared by the laboratories participating in the study.

Cervical Cancer Prevention: From DNA to mRNA? - New Technologies for Cervical Cancer Screening 2

HPV as Primary Screening Test in Cervical Cancer Prevention: From DNA to mRNA? A Randomised Controlled Trial Nested in a Double Testing Study With Long Term Follow up

Sum of CIN2+ detected in women with positive DNA and negative mRNA or p16 tests during the entire period (5 years) divided by the total number of CIN2+ found in the study. The HPV DNA test will be the final follow-up test, since it is the most sensitive test among the candidates for screening, so it is the one that allows to estimate more accurately the prevalence of lesions.

proportion of CIN2+, HPV DNA positive and p16 or mRNA negative, which regress in a year

measure of how much the cytological triage can reduce overdiagnosis compared to HPV DNA with direct sending to colposcopy

direct comparison of the effectiveness between a screening based on the HPV mRNA or p16 test followed by cytological triage and a screening with direct sending to colposcopy

Azienda Unità Sanitaria Locale Reggio Emilia

Digestive System Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Carcinoma in Situ

Hyperplasia

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Pharmaceutical Solutions

All Drugs and Chemicals

Anti-Infective Agents

Central Nervous System Depressants

Micronutrients

Coagulants

Ethanol

Iodine

Lugol's solution

Cadexomer iodine

This opportunistic screening cohort is constructed among patients aged 45-69 years who undergo endoscopic examinations at the endoscopy center in any of the five hospitals included in this study. Enrolled participants are requested to complete a computer aided one-on-one questionnaire regarding demographic factors, smoking and alcohol drinking status, dietary habits，digestive tract symptoms and family history of ESCC. Then experienced endoscopists will perform the upper gastrointestinal endoscopic examination for each participant, and the entire esophagus will be visually examined with the white light, NBI and iodine staining endoscopic examination.

Participants' esophagus will be examined by three commonly used diagnostic techniques in the order of : 1. White light endoscopy (WLE); 2. Narrow Band Imaging (NBI) and 3. Iodine Staining Endoscopy (ISE) with 1.2% Lugol's iodine solution. The required observation time is no less than 1 minute for WLE and 2 minutes for NBI and ISE. Endoscopic images of each participant are routinely captured at every 5 centimeters in the esophagus, and information is recorded in detail for each focal lesion. Biopsies are taken from all visually abnormal areas found by any one of the three techniques, histopathologic diagnoses are rendered by two pathologists according to standard criteria and discrepancies are adjudicated by consultation. The recorded endoscopic images for each biopsied lesion are read by two trained researchers and the visualized feature of lesions are decomposed into several indicators (e.g. size, shape, color, and border of lesions) .

Endoscopic examination using white light, NBI and iodine staining

Yang Ke, MD

Zhonghu He, PhD

Fandong Meng, MD

Yi Guo, MD

Anxiang Liu, MD

Yujie He, MD

Shengjuan Hu, MD

Mengfei Liu, PhD

The investigators aim to evaluate the performance of Narrow Band Imaging (NBI) endoscopy in Esophageal Squamous Cell Carcinoma (ESCC) screening, as compared to the currently used White Light Endoscopy (WLE) and Lugol's Iodine Staining Endoscopy (ISE). NBI is a simple, safe and non-invasive technique, which can provide real-time optical staining for suspicious lesions. This trial is designated to enroll 10000 participants from five centers located in different regions (North, West and South) in China, which would provide real-world evidence for the recommendation of endoscopic diagnostic technique used in ESCC screening projects.

Performance of White Light, NBI and Iodine Staining Endoscopy in the Diagnosis of Esophageal Lesions

Performance of White Light, Narrow Band Imaging and Iodine Staining Endoscopy in the Diagnosis of Esophageal Squamous Epithelium Lesions: A Multicenter Clinical Study in China

Sensitivity of WLE, NBI and ISE, taking results from histopathological analysis of the biopsy specimens as the golden standard.

Specificity of WLE, NBI and ISE, taking results from histopathological analysis of the biopsy specimens as the golden standard.

PPV of WLE, NBI and ISE, taking results from histopathological analysis of the biopsy specimens as the golden standard.

NPV of WLE, NBI and ISE, taking results from histopathological analysis of the biopsy specimens as the golden standard.

The estimated odds ratio of each decomposed graphic abnormal features of lesions, taking "severe dysplasia and above" diagnosed via histopathological analysis as the outcome events.

The area under the curve (AUC) of visualized graphic abnormal features for predicting severe dysplasia and above lesions.

Peking University Cancer Hospital & Institute

Professor

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Cervical Cancer Prevention: From DNA to mRNA? - New Technologies for Cervical Cancer Screening 2	NCT01837693	Precancerous Co... Neoplasms	Experimental: i...	25 Years - 59 Years	Azienda Unità Sanitaria Locale Reggio Emilia
Performance of White Light, NBI and Iodine Staining Endoscopy in the Diagnosis of Esophageal Lesions	NCT04170257	Mild Dysplasia ... Moderate Dyspla... Severe Dysplasi... Carcinoma in Si... Esophageal Squa...	Endoscopic exam...	45 Years - 69 Years	Peking University Cancer Hospital & Institute

Spots Global Cancer Trial Database for sensitivity and specificity