Neoplasms

All Conditions

Mouth and Tooth Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Mouth Neoplasms

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Oral Squamous Cell Carcinoma

Oral Cancer

Lip and Oral Cavity Cancer

Herbal and Botanical

All Drugs and Chemicals

Raspberry

Drug consisting of 10% FBR containing bioadhesive gel. Participants instructed to apply 0.5 gm of 10% FBR containing bioadhesive gel four times a day to lesional site

Color/consistency matched placebo (no black raspberry) gel

0.5 gm applied 4 times daily to the oral premalignant lesion site for a duration of 3 months

10% FBR containing bioadhesive gel

placebo gel

Susan R Mallery, DDS, PhD

This is a multicenter placebo-controlled clinical trial to assess the effects of a topically applied gel on precancerous oral epithelial lesions. A total of 41 participants will be enrolled in this trial, and 22 of them will be enrolled at Ohio State. \[The remaining 19 participants will be enrolled at the University of North Carolina (9 participants) and the University of Louisville (8 participants)\]. At all three institutions, half of the participants will randomly be assigned to the 10% FBR gel (0.5 gm four times daily for 3 months), while half will enter the placebo control arm. All trial participants will have a pretreatment (including lesional and perilesional tissue) biopsy taken before and an excisional biopsy after 3 months of treatment. As pretreatment indices are compared to post treatment effects on each patient, patients serve as their own internal control. Pretreatment lesional biopsies are obtained to establish a pretreatment diagnosis and provide a pretreatment baseline for the experimental parameters.

Forty one (41) patients with microscopically confirmed premalignant oral epithelial disease (epithelial dysplasia) will be enrolled in this trial at three clinical centers, i.e. the Ohio State University, University of North Carolina at Chapel Hill and University of Louisville. At all three institutions, half of the participants will randomly be assigned to the 10% FBR gel (0.5 gm four times daily for 3 months), while half will enter the placebo control arm.

In accordance with the established standard of care, all participants need to have biopsies taken of their suspicious oral lesions to establish the diagnosis (non research). Trial participants will have three total biopsies. Pretreatment biopsies will entail: 1) perilesional tissue and single saliva sample for FBR metabolic profiling studies (tissue and saliva will be obtained 15 minutes after a single 0.5 gm application of 10% FBR gel for metabolic profiling. Gel application and nonlesional biopsy will be obtained before incisional biopsy of lesional tissue), and 2) a hemisection of lesional tissue to establish a diagnosis and provide a pretreatment baseline for the experimental parameters. While the pretreatment biopsy includes removal of both perilesional and lesional tissue, there will only be one surgical wound as the perilesional tissue is contiguous with the lesional tissue. A final excisional biopsy of the treatment site including any remaining residual lesional tissue (excision of oral dysplastic lesions is consistent with current standards of care) will be obtained after 3 months of treatment. The experimental design permits each patient to serve as their own internal control. Briefly, these following parameters will be monitored in all participants (comparisons made relative to patient-matched pretreatment to posttreatment biopsies): 1) light microscopic diagnoses, 2) clinical appearances and lesional sizes, 3) microarray gene expression analyses, 4) microvascular densities of superficial connective tissues, 5) LOH indices at loci associated with tumor suppressor genes, 6) intraepithelial levels of COX-2 and iNOS protein (image analysis quantified immunohistochemistry), 7) comparison of FBR metabolic profiles relative to extent of chemopreventive efficacy noted.

Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention

A hemisection of lesional tissue will be conducted before the 3 month treatment to establish a diagnosis and provide a pretreatment baseline for the experimental parameters. Anl excisional biopsy of the treatment site including any remaining residual lesional tissue (excision of oral dysplastic lesions is consistent with current standards of care) will be obtained after 3 months of treatment to provide a posttreatment diagnosis. The 0 to 8 histologic scale was:0=normal with or without hyperkeratosis BEST OUTCOME, 1=atypia, 2=mild dysplasia, 3=mild-moderate dysplasia, 4=moderate dysplasia,5=moderate-severe dysplasia,6=severe dysplasia, 7=carcinoma in situ, 8=invasive oral squamous cell carcinoma (WORST OUTCOME).

The remaining oral dysplasia lesion will be inspected at each follow up appointment (every 10-14 days). Biopsies will be immediately conducted on patients with any indication of malignant transformation including indurated, rolled borders, nonhealing ulcers, etc. Accordingly, these patients will withdraw from the trial. Participants will also be monitored for any changes consistent with contact mucositis e.g. soreness and erythema at application site. Clinical photographs were taken for the patients records. Pre treatment and post treatment photographs, with a ruler in place, were used for accurate pre and post treatment size measurement. NOTE: if treatment is beneficial, lesional size will decrease which will be reflected as a negative number.

Laboratory experiments will be conducted to assess the effects of gel treatment on pre and post loss of heterozygosity (LOH) events at loci associated with tumor suppressor genes.

University of Louisville

University of North Carolina, Chapel Hill

National Cancer Institute (NCI)

Ohio State University

Professor

Active 10% FBR containing bioadhesive gel

Bioadhesive 10% freeze-dried black raspberry gel: 0.5 gm applied 4 times daily to the oral premalignant lesion site for a duration of 3 months

No adverse events

10% FBR Gel

Color/consistency matched placebo (no black raspberry) gel

Color/consistency matched placebo gel: 0.5 gm applied 4 times daily to the oral premalignant lesion site for a duration of 3 months

No adverse events

Placebo Gel

Active 10% FBR containing bioadhesive gel

Bioadhesive 10% freeze-dried black raspberry gel: 0.5 gm applied 4 times daily to the oral premalignant lesion site for a duration of 3 months

Color/consistency matched placebo (no black raspberry) gel

Color/consistency matched placebo gel: 0.5 gm applied 4 times daily to the oral premalignant lesion site for a duration of 3 months

Total

The patients were randomly assigned by computer generated numbers to either the BRB or the placebo gel groups.

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

While we initially planned to include microvascular densities and COX-2 analyses, there were insufficient tissue samples to collect these data. Therefore as we do not have these data we can not report them.

Susan R, Mallery DDS, PhD

Wilcoxon matched-pairs signed rank test (intrapatient pre versus post treatment scores)

Wilcoxon matched-pairs signed rank test (pre versus post treatment scores)

Pretreatment

Posttreatment

The population evaluated were as previously described i.e. 22 participants in the BRB gel cohort and 18 participants in the placebo gel cohort.

Light Microscopic Histologically Scored Diagnoses Pretreatment to Post Treatment

Active 10% FBR containing bioadhesive gel

Bioadhesive 10% freeze-dried black raspberry gel: 0.5 gm applied 4 times daily to the oral premalignant lesion site for a duration of 3 months.

Changes in Lesional Sizes

Treatment Changes in Loss of Heterozygosity Events

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Uterine Cervical Neoplasms

Carcinoma in Situ

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Cervical Intraepithelial Neoplasia

Device: Self-sampling swab from Eve Medical for collection of vaginal cells.

Device: Regular polyester swab for collection of vaginal cells.

Routine colposcopy sample collected by a physician.

The Eve collection system is a plastic device not much bigger than a tampon that is inserted in the vaginal cavity. A silicone brush is then swiped around the vagina to scrape a few vaginal cells for cervical cancer screening.

Eve Medical self-collection system©

Regular polyester swab for collection of vaginal cells.

cobas® PCR Female swab self-sampling

Physician-collected sampling

Eduardo Franco, DrPH

Mariam El-Zein, PhD

The proposed study seeks to compare the diagnostic performance of Human Papillomavirus (HPV) testing in self-collected samples via the Eve Medical self-collection system© (Eve) with standard physician-collected samples for the detection of cervical intraepithelial neoplasia grade 1 or worse (CIN1+) and cervical cancer among women referred for colposcopy. The performance of the Eve sample will also be compared with that of a second self-sample via a cobas® PCR Female swab.

Approximately 1000 adult women with an abnormal Pap test at the level of an atypical squamous cells of undetermined significance or worse squamous or glandular abnormality (i.e., ASCUS+) or an abnormal co-test (ASCUS+ and HPV-positive) result will be recruited over a period of 12 months via colposcopy clinics located at the Jewish General Hospital, St-Mary's Hospital, and the McGill University Health Centers (Royal Victoria Hospital).

Participating women will undergo three cervical or cervicovaginal sampling techniques: 1) self-sampling using the Eve Medical self-collection system©; 2) self-sampling using a cobas® PCR Female swab; and 3) physician-collected sampling. The participants will also fill in a questionnaire on their experience with the convenience and acceptability of the Eve system, relative to the other two sampling approaches. The decision as to which self-sample is to be collected first will be dependent on randomization

HPV testing will be done using the cobas® 4800 HPV Test. The liquid medium of within the cobas® PCR CELL Collection Media with the provider collected sample and the cobas® PCR media with the two self-collected samples will be used to suspend the cellular material prior to HPV testing. We have made collaborative arrangements with Dr. Marcel Behr, Chief of the Department of Clinical Microbiology at the McGill University Health Centre for the HPV genotyping work.

Histology-confirmed CIN1+ will form the study outcome or case definition. Sensitivity, specificity, and predictive values (along with their respective 95% confidence intervals) will be calculated for each sample type to evaluate the clinical performance of the various sampling techniques. We will use CIN1+ as definition of disease but analyses will also be performed for more stringent definitions, e.g. CIN2+ or CIN3/cancer.

After the discovery that Human Papillomavirus (HPV) infection is the necessary cause of cervical cancer there have been much interest in the introduction of novel screening strategies involving HPV DNA testing \[1\]. HPV DNA testing was shown to have higher sensitivity in detecting cervical cancer and its precursors and greater reproducibility than Papanicolaou (Pap) cytology screening and has been therefore proposed as the primary screening method for the future. In high-income countries, cases of cervical cancer continue to develop among unscreened and under-screened women \[2\]. Factors discouraging women from attending routine screening include fear of pain or discomfort, lack of time or perceived inconvenience, cultural or religious concerns, and poor socioeconomic status \[3\]. For a screening program to be effective high coverage is essential and thus attendance is a critical requirement.

Because of the high sensitivity of molecular HPV testing to detect cervical cancer precursors there is great potential for screening coverage to be increased by inviting non-attendant to provide self-collected vaginal samples. Providing these women with a simple, convenient, and inexpensive means of self-testing may improve cervical screening participation \[3\]. Self-sampling is also an attractive approach to assist screening in poor countries, which typically do not have structured cervical cancer screening programs while having to bear the greatest burden of cervical cancer morbidity and mortality \[4\]. Self-sampling can also enhance the value of post-HPV vaccination surveillance by allowing a more efficient monitoring of HPV type distribution in populations. Finally, self-sampling represents a good research tool to assist prospective studies of genital HPV infection and natural history of cervical neoplasia.

Specifically for cervical cancer screening, it has been shown that self-collected cervicovaginal specimens from women who received proper instruction for collecting them yield HPV test results that are comparable to those in specimens collected by physicians \[5-8\]. Women also prefer self-sampling relative to clinician-provided samples, provided that they can be assured that they are told how to properly collect the sample \[8, 9\]. Although there is conceivably some loss of sensitivity and specificity in screening for cervical cancer in a specimen that is not directly collected from the ecto- and endo-cervix the overall accuracy of the HPV testing results (to identify presence of cervical precancerous lesions) is still superior to that of physician-collected Pap smears. Therefore, replacing a more anatomically-correct specimen (the one collected with direct visualization of the cervix by a primary healthcare provider) with one collected from the vagina (and thus diluted with exfoliated cells from a wider epithelial surface area) is compensated by the high sensitivity of the molecular screening approach \[6, 10, 11\]. Performance of screening seems also to be unaffected by storage and transport of the self-sample swabs, irrespective of whether they have been kept dry or transferred and resuspended into a liquid transport medium \[10, 12\].

A critical feature in enhancing women's acceptance and adherence with the self-sampling approach for cervical cancer screening and HPV surveillance studies is the convenience of the device used for collection. Dacron and polyester swabs are simple, common, and inexpensive. However, they are inconvenient and not isolated within a sheath that prevents contact of the sampling area with mucosal surfaces in the labia and vaginal opening. Ideally, sampling devices should be anatomically correct to facilitate insertion and the sampling surface that will retain the exfoliated cells should be protected from contact with the labia and lower vaginal mucosa while the device is inserted, with the objective of sampling cells that are mostly from the cervix and upper vaginal area.

HPV DNA testing using self-collected cervicovaginal specimens represents a promising strategy to increase cervical screening participation and thus reduce rates of cervical cancer in countries with established cervical screening programs. Furthermore, this approach can also greatly improve the coverage and quality of cervical cancer screening in developing countries, as well as in remote regions in developed countries, e.g., aboriginal populations in Northern Quebec and in First Nations territories. Facilitating and improving uptake of cervical cancer screening would save lives, reduce costs of treating invasive cancer and potentially reduce inequalities in avoidable mortality caused from cervical cancer.

(full protocol available upon request)

Cervical And Self-Sample In Screening Study

Cervical And Self-Sample In Screening (CASSIS) Study: Diagnostic Performance of Molecular HPV Testing With the Eve Medical Self-collection System© for Detecting Cervical Intraepithelial Neoplasia

Diagnostic accuracy (sensitivity and specificity with 95% confidence intervals, and predictive values will be determined for each sample type to evaluate the clinical performance of the various sampling techniques. The investigators hypothesize that the Eve sample will yield sensitivity and specificity results that are no worse than those with the physician-collected sample, while providing better or equivalent results than those with the self-sample based on the Cobas® PCR Female swab.

Participants will be asked to fill out a questionnaire consisting of 10 questions on ease of use, comfort, embarrassment, and clarity of instructions when using self-sampled cervicovaginal sampling such as the HerSwabTM and the female polyester swab as compared to the physician-collected sample. The investigators hypothesize similar patient satisfaction with the three sampling approaches.

McGill University

James McGill Professor in the Departments of Oncology and Epidemiology & Biostatistics, Director, Division of Cancer Epidemiology, and Chairman, Department of Oncology, at McGill University's Faculty of Medicine

Symptoms and General Pathology

Digestive System Diseases

Atrophy

Gastritis, Atrophic

Gastritis

Pathological Conditions, Anatomical

Gastroenteritis

Gastrointestinal Diseases

Stomach Diseases

Chronic Graft Versus Host Disease

Subjects taking prepared Fuzhegn Nizeng granules twice daily for 6 month.

Fuzhegn Nizeng Decoction

Subjects taking prepared Moluodan granules 9g twice daily for 6 month.

Moluodan granules

Xuezhi Zhang, Doctor

Fuzheng Nizeng Formula (FZNZ) is derived from the classic formula Liujunzi Decoction. Former pilot study found that FZNZ promoted the recovery of gastric atrophy and relieve the relative symptoms. This study is to evaluate its efficacy for chronic atrophic gastritis with low-grade intraepithelial neoplasia, compared with positive control Molduodan granule.

Fuzheng Nizeng Formula for Chronic Atrophic Gastritis With Low-grade Intraepithelial Neoplasia, a Multicenter Randomized Controlled Trial

Fuzhegn Nizeng Formula for Chronic Atrophic Gastritis With Low-grade Intraepithelial Neoplasia, a Multicenter Randomized Controlled Trial

Stomach biopsy will be taken after drug administration completion.

Dyspepsia symptoms will be recorded and evaluated by 7-point Global Overall Symptom Scale

Peking University First Hospital

Barrett Esophagus

Precancerous Conditions

Esophageal Diseases

Oculocerebral Syndrome With Hypopigmentation

Anti-Infective Agents

Proflavine

Anti-Infective Agents, Local

proflavine

The overall objective of this pilot study is to determine whether multispectral imaging increases the diagnostic accuracy of the current standard of high-definition white-light endoscopy for the detection of Barrett's-associated neoplasia (high grade dysplasia or cancer). The investigators goal is to develop a multispectral endoscopic platform that can be used to survey a large surface area and, potentially, serve as a 'red flag' for microendoscopic imaging of small areas. The goal of this pilot study is to preliminarily determine the accuracy of these modalities during the endoscopic surveillance of Barrett's esophagus.

Endoscopic Multispectral Imaging for the Early Detection of Barrett's Neoplasia

William Marsh Rice University

Anandasabapathy, Sharmila, M.D.

Uterine Cervical Dysplasia

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

Antineoplastic Agents

Vitamins

Acetic Acid

Retinol acetate

HRME will capture images from all areas considered abnormal by VIA (visual inspection with acetic acid) and/or colposcopy. In addition, all four quadrants will be probed with HRME to ensure that any non-acetowhite lesions are also observed

HRME will capture images from all areas considered abnormal by VIA and/or colposcopy. In addition, all four quadrants will be probed with HRME to ensure that any non-acetowhite lesions are also observed

HRME examination

Jose H Fregnani, PhD

Rui M Reis, PhD

STUDY PURPOSES: This study aims to evaluate a high resolution microendoscope (HRME): 1) To assess the sensitivity and specificity of the HRME device in the detection of cervical intraepithelial neoplasia grade 2 (CIN2) or histologically more severe lesion (NIC2+) and cervical intraepithelial neoplasia grade 3 (CIN3) or histologically more severe lesion (NIC3+) in a comprehensive case-by-case basis; 2) Compare the accuracy of the HRME device with acetic acid visualization (VIA) and colposcopy. METHODOLOGY: 1,780 women with abnormal Pap Smears (ASCUS+) or positive high-risk human papillomavirus (HPV) test in the cervix performed in the Barretos Cancer Hospital (HCB, Barretos, Brazil) screening program will be recruited, either at Mobile Prevention Units or Fixed Units, who have been referred for diagnostic investigation with colposcopy. The invitation for women to participate in the study will be made immediately before the medical consultation for colposcopy, in the Prevention Department of Barretos Cancer Hospital. Women who decide to participate in this study will sign an Informed Consent Form after invitation and relevant explanations, which will be provided by the researcher in charge or by a representative with previous training appointed by him for the application of the Form in question. During the colposcopy examination, the HRME device will be used to check the presence of precursor lesions in the cervix. HRME will capture images from all areas considered abnormal by VIA and/or colposcopy. Any abnormal areas detected by VIA and/or colposcopy will undergo a biopsy. If no abnormal area is observed, a cervical microbiopsy will be obtained from an apparently normal area examined using HRME. If during the study a precursor disease or cervical cancer is detected in any woman, an appropriate treatment will be offered by Barretos Cancer Hospital according to an institutional protocol.

STUDY DESIGN:

This is an experimental methodological study with a single-arm, unmasked, unicentric, international diagnostic device.

OUTLINES:

1,780 women with abnormal Pap Smears (ASCUS+) or positive high-risk HPV test in the cervix performed in the Barretos Cancer Hospital (HCB, Barretos, Brazil) screening program will be recruited, either at Mobile Prevention Units or Fixed Units, who have been referred for diagnostic investigation with colposcopy. During the colposcopy examination, the HRME device will be used to check the presence of precursor lesions in the cervix.

PRE-TESTING VERIFICATION:

As this research may include cervical biopsy in women with fertility, for safety reasons, the possibility of pregnancy in this group of women will be verified, since biopsy performed in the cervix of pregnant woman increases the risk of abortion. This verification will be performed by means of clinical history (menstrual delay, signs suggesting pregnancy, contraceptive methods, etc.) and also by means of qualitative research on human chorionic gonadotropin in urine. This test is also known as "rapid pregnancy test" or "pharmacy test", with an extensive list of products sold in Brazil and authorized by "Agencia Nacional de Vigilancia Sanitária" (ANVISA, Brazilian Agency of Health Surveillance). The principle of the test involves a single step immunochromatographic method to detect the hormone. Reaction occurs on a reagent strip, where a small amount of urine is deposited. Test result is provided in approximately 2 minutes. Women who are pregnant (or suspected to be pregnant) will not be included in the study, but will be submitted to diagnostic investigation according to the institutional protocol for pregnant women with changes in the cervix at HCB. These women will receive medical orientation and will be referred to a specialized obstetrical service.

COLLECTION OF CERVICAL CYTOLOGY:

Before the diagnostic examinations are performed, the doctor will collect a new cervical cytology (Papanicolaou), which is part of the routine of the Department of Colposcopy for every woman who has an altered Pap Smear or positive HPV test. These samples will be preserved in an ethanol-based preservative medium (SurePath™ Preservative Fluid, Becton \& Dickinson, USA) and will be sent to the Department of Pathology of HCB where they will undergo an automated processing for the preparation of cytology slides.

DIAGNOSTIC EXAMINATIONS:

VIA will be performed using 3-5% acetic acid, applied on the cervix and to any abnormal lesions observed. Then, iodine solution will be applied, and the colposcopy will be performed. It is necessary to clarify that the application of acetic acid and iodine is routinely performed during a standard colposcopy examination.

Then, Proflavine (0.01%) will be applied to the surface of the cervix. HRME will capture images from all areas considered abnormal by VIA and/or colposcopy. In addition, all four quadrants will be probed with HRME to ensure that any non-acetowhite lesions are also observed. The person responsible for the colposcopy will take note of your opinion about the lesion and HRME image at each area (normal, benign, low-grade precancerous, high-grade precancerous or cancer). The complete HRME imaging procedure will add 5-10 minutes to the standard colposcopy examination. Observations related to VIA, colposcopy and HRME will be registered by quadrant. Any abnormal areas detected by VIA and/or colposcopy will undergo a biopsy. If no abnormal area is observed, but the woman has an altered cytology test or a positive HPV test, a cervical microbiopsy will be obtained from an apparently normal area captured by HRME imaging of that area. For all cervical biopsies, special tweezers will be used, causing minimal tissue trauma (microbiopsy) and reducing participant discomfort. These tweezers are different from those commonly used in colposcopy tests, which usually perform biopsies on large areas and bring more discomfort to women.

Two experienced HCB pathologists, ignoring all study results, will review histology and classify areas as normal, cervical intraepithelial neoplasia grade 1 (CIN 1), CIN 2, CIN 3, adenocarcinoma in situ (AIS) or cancer according to standardized criteria. Conflicting results will be resolved by means of consensus review among pathologists.

HIGH-RISK HPV SCREENING AND GENOTYPING:

High-risk HPV screening will be performed on aliquots of cervical cytology samples (SurePath™) collected just prior to colposcopy in women who have not been submitted to this test yet. HPV test will be performed on a Cobas X480 ™ device (Roche Molecular Systems, USA), which is available at the technology park of the Molecular Oncology Research Center of Barretos Cancer Hospital - Pio XII Institution. The test protocol will be performed as described by the manufacturer.

COBAS system is an automated amplification device (by means of real time polymerase chain reaction (PCR)) for the detection of 14 high-risk HPV types (16, 18 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68), and can process up to 94 simultaneous samples. Tests which detected high-risk non-16 and non-18 HPV will be submitted to complementary analysis to identify genotype(s) using the linear array technique, since COBAS system does not provide genotyping of these high-risk HPVs. For this purpose, linear array HPV genotyping (CE-IVD) Test for HPV Genotyping kit (Roche Molecular Systems, USA) will be used.

DATA ANALYSIS:

The primary endpoint is the diagnosis rate of CIN2+ and CIN3+. Sensitivity and diagnostic specificity of VIA, colposcopy and HRME based on each lesion and each patient using histological diagnosis as gold standard will be calculated assuming lesions diagnosed as CIN2 + or CIN3 + are positive. Sensitivity and specificity of VIA and colposcopy will also be calculated as a comparison method.

A case-by-case description will be made using descriptive statistics. Categorical variables will be compared by means of the chi-square test or Fisher's exact test, depending on the expected values in the contingency tables. To compare numerical variables, the t-tests or the Mann-Whitney test will be used depending on the adherence to normality (to be verified by the Kolmogorov-Smirnov test).

SAMPLE SIZE CALCULATION:

Sample calculation was based on information from other studies of the same group (including data not yet published). The following premises were taken: HRME sensitivity and specificity for CIN2+ diagnosis (93% and 48%, respectively, per biopsy area) and prevalence of CIN2+ in the colposcopy clinic of HCB (ranging from 20 to 30%). Considering a prevalence of disease of 25% , it is estimated that it will be necessary to include 1,424 women (625 cases for sensitivity calculation and 799 cases for specificity calculation) to reach the expected sensitivity and specificity rates with a maximum margin of error of 4% for a 95% confidence interval. Considering an estimated loss of 10-15% (non-attendance for colposcopy examination and HRME), the corrected sample estimate will range from 1,566 to 1,637 women. Therefore, the study intends to include 1,600 women with abnormal cervical cytology or positive HPV test. Additionally, a group of women with no change in cervical cytology and HPV test will be invited to participate in the research in order to check verification bias. This bias occurs when only the positive cases in the screening are selected to perform complementary diagnostic examinations, overestimating the sensitivity and underestimating the specificity. It is recommended that a percentage of negative cases be verified according to the standard gold examination. Therefore, 10% of the study population will consist of negative cases in both cervical cytology and the HPV test, which corresponds to nearly 180 cases. Thus, the final sample estimate will be of 1,780 women, of whom 1,600 women will have screening (altered cytology or positive HPV test) results reported as positive and 180 will have screening results reported as negative (negative cytology and HPV test).

STUDY SCHEDULE:

The study will last 3 years.

HRME in the Screening of Cervical Cancer Precursor Lesions in Brazil (UH3 - Brazil)

Validation of High Resolution Microendoscope in the Screening of Cervical Cancer Precursor Lesions in Brazil (UH3 - Brazil)

RedCap Platform will be used to share data.

Sensitivity and Specificity of CIN2+ and CIN3+ detection using HRME

Comparison of sensitivity and specificity of CIN2+ and CIN3+ with colposcopy and VIA

M.D. Anderson Cancer Center

Barretos Cancer Hospital

Colitis

Colitis, Ulcerative

Ulcer

Colonic Diseases

Intestinal Diseases

Inflammatory Bowel Diseases

Endomicroscope

Peter R. Galle, MD PhD

Timely diagnosis of intraepithelial neoplasias (premalignant condition)is of crucial importance for clinical management of ulcerative colitis. We assessed the value of combined chromoscopy and endomicroscopy for diagnosis of intraepithelial neoplasias in a randomised controlled trial.

Endomicroscopy is a new device which enables microscopy of the mucosal layer during ongoing colonoscopy. Chromoscopy means topical staining of mucosal surface to unmask areas of interest, which are subsequently examined with the endomicroscopic system.

Ulcerative colitis (UC) is an immune cell-mediated inflammatory bowel disease characterized by mucosal ulcerations, rectal bleeding, diarrhea, and abdominal pain. Patients with long standing UC face an increased risk for development of colitis associated colorectal cancer. Factors associated with increased risk for cancer development include the duration of the disease, extensive colonic involvement (pancolitis, backwash ileitis), primary sclerosing cholangitis and severe chronic active inflammation. Based on these observations, colonoscopic surveillance in patients with long-standing UC is highly recommended.

The main objective of surveillance colonoscopy in UC is to detect neoplasia at a surgically curative and preferably pre-invasive stage. However, in contrast to sporadic colorectal cancer, the growing pattern of neoplastic tissue in UC is often flat and multifocal. Therefore, significant lesions during conventional colonoscopy in UC are frequently overlooked. Chromoscopy with topically applied dyes such as methylene blue or indigo carmine facilitates the endoscopic detection of flat, circumscribed colitis associated neoplastic changes in UC. In fact, five controlled studies showed that the diagnostic yield for the detection of intraepithelial neoplasia (IN) using chromoscopy is higher as compared to conventional colonoscopy with random biopsies. Based on the above studies, chromoscopy has recently been considered for incorporation into US guidelines for surveillance of patients with long-standing UC. However, although this technique does allow identification of mucosal lesions, it is not suitable for accurate endoscopic diagnosis of intraepithelial neoplasias in UC due to the lack of cellular resolution and subsurface imaging. For endoscopy, novel techniques allowing accurate diagnoses during ongoing examination are highly desirable and may allow appropriate and immediate therapeutic manoeuvres (e.g. resection versus biopsy). Recently, a miniaturized confocal microscope has been developed integrated in the distal tip of a conventional colonoscope . This new diagnostic technology for gastrointestinal endoscopy, denoted confocal endomicroscopy, enables histological evaluation of the mucosal layer during ongoing colonoscopy. Furthermore, in patients screened for sporadic colorectal cancer, surface and subsurface analysis at cellular and subcellular resolution can be used to predict intraepithelial neoplasias (INs) with high accuracy. However, due to the time required for examination of large surface areas, this technique is not suitable for screening of the entire colonic surface in UC to detect neoplasias in flat mucosa.

In the present study, we employ chromoscopy to identify potential neoplastic lesions and combine this for the first time with endomicroscopy for the endoscopic diagnosis of colitis associated intraepithelial neoplasias in UC. Using such chromoscopy guided endomicroscopy we will ecaluate whether the diagnostic yield diagnosing IN can be significantly increased.

Chromoscopic Guided Endomicroscpy to Diagnose Colitis Associated Dysplasia

Diagnosis of Intraepithelial Neoplasia in Patients With Long Standing Ulcerative Colitis With Chromoscopic Guided Endomicroscopy

Johannes Gutenberg University Mainz

Women aged 30 to 64 years who attend the Cervical Cancer Screening Program in 100 health centers in the state of Tlaxcala, Mexico

All cervical and/or vaginal specimens are tested for hrHPV using the Cobas® 4800 HPV test. Triage testing will be performed on all participants with a positive HR-HPV test declared consent at recruitment visit: HPV16/18 genotyping, Cobas® 4800 HPV test, HPV16/18/45 genotyping, BD OnclarityTM HPV Assay, OncoE6 Cervical Test, Liquid based cytology with Papanicolaou stain and p16INK4a/ Ki-67 immunostain.

HPV screening and triage tests

Jorge Salmerón, MD DSc

Jorge Salmerón, DSc

Eduardo C Lazcano-Ponce, MD DSc

While there is broad consensus that HR-HPV detection is the best available primary screening test, there is no agreement about the most efficient and reliable triage procedure for HR-HPV positive women. Transient HR-HPV infections are very common, and the vast majority of these infections spontaneously regress after a year or two. Only a small fraction of cases will lead to persistent infection responsible for cervical neoplasia. The FRIDA Study is a large, population-based study that was designed to evaluate the performance and cost-effectiveness of different triage strategies for hrHPV-positive women in Mexico.

The target population is over \<100,000 women aged 30 to 64 years who attend the Cervical Cancer Screening Program in 100 health centers in the state of Tlaxcala, Mexico. All women will be evaluated to determine hrHPV infection using the Cobas® 4800 HPV test. Triage strategies will be performed as reflex tests in all hrHPV-positive participants: HPV-16/18/45 genotyping, detection of the E6 oncoprotein of HPV-16/18, cytology, and immunocytochemistry using p16INK4a/Ki67. Women with at least one positive triage test will be referred for colposcopy evaluation, where a minimum of four biopsies and an endocervical sample are systematically collected. Histological confirmation will be performed by a standardized panel of pathologists.

Two cervical samples will be collected using a Cervex-Brush® (Rovers®). The first collected sample will be placed in a vial containing BD CytoRich™ preservative (BD Diagnostics, Burlington, NC), and the second sample will be placed in a ThinPrep® vial (Hologic, Inc., Bedford, MA). Both samples will be temporarily stored at room temperature at the health center until they are delivered to the lab facilities. Women who refuse a pelvic examination will be offered the option to self-collect a vaginal sample at the health facility or at their home that can be used for hrHPV testing. Only HR-HPV positive participants will move onto the cytology/molecular triage testing phase. After triage procedures, all remaining samples collected in either of the vials from HR-HPV positive women will be stored independently for additional analysis as required by the study procedures.

Triage Strategies in Cervical Cancer Prevention

Molecular Triage in Cervical Cancer Prevention: The Tlaxcala Study

All women will be colposcopically evaluated in order to rule out any clinically evident invasive cancer. In cases of invasive cancer, patients will be referred to onco-gynecology services immediately. Before biopsy collection, endocervical sampling is performed using an Endocervex Brush®. A minimum of four biopsies are collected, at least one per quadrant, from the more suspicious area on cervical transformation zone. Histological evaluation of all samples (biopsies and/or endocervical curettage samples) will be evaluated for final diagnosis and confirmation of CIN2+ cases by two pathologists according to Mexico's Cervical Cancer Screening Programme's guidelines. An external expert-pathologist, will resolve discrepancies and render a final decision.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention	NCT01192204	Squamous Cell C... Intraepithelial...	10% FBR contain... placebo gel	21 Years - 80 Years	Ohio State University
Cervical And Self-Sample In Screening Study	NCT02397252	Cervical Cancer Intraepithelial...	Eve Medical sel... cobas® PCR Fema... Physician-colle...	-	McGill University
Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention	NCT01192204	Squamous Cell C... Intraepithelial...	10% FBR contain... placebo gel	21 Years - 80 Years	Ohio State University
Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention	NCT01192204	Squamous Cell C... Intraepithelial...	10% FBR contain... placebo gel	21 Years - 80 Years	Ohio State University
Clinical Evaluation of Bioadhesive Gels for Oral Cancer Chemoprevention	NCT01192204	Squamous Cell C... Intraepithelial...	10% FBR contain... placebo gel	21 Years - 80 Years	Ohio State University
Fuzheng Nizeng Formula for Chronic Atrophic Gastritis With Low-grade Intraepithelial Neoplasia, a Multicenter Randomized Controlled Trial	NCT06324825	Atrophic Gastri...	Fuzhegn Nizeng ... Moluodan granul...	18 Years -	Peking University First Hospital
Endoscopic Multispectral Imaging for the Early Detection of Barrett's Neoplasia	NCT01384864	Barrett's Esoph... Intraepithelial...	proflavine	18 Years -	Anandasabapathy, Sharmila, M.D.
HRME in the Screening of Cervical Cancer Precursor Lesions in Brazil (UH3 - Brazil)	NCT03195218	Intraepithelial... Intraepithelial... Cervical Cancer Neoplasm Cervix	HRME examinatio...	18 Years -	Barretos Cancer Hospital
Chromoscopic Guided Endomicroscpy to Diagnose Colitis Associated Dysplasia	NCT00352404	Ulcerative Coli... Intraepithelial... Cancer	Endomicroscope	18 Years - 80 Years	Johannes Gutenberg University Mainz
Triage Strategies in Cervical Cancer Prevention	NCT02510027	Cervical Cancer Intraepithelial...	HPV screening a...	30 Years - 64 Years	Instituto Nacional de Salud Publica, Mexico
Chromoscopic Guided Endomicroscpy to Diagnose Colitis Associated Dysplasia	NCT00352404	Ulcerative Coli... Intraepithelial... Cancer	Endomicroscope	18 Years - 80 Years	Johannes Gutenberg University Mainz

Spots Global Cancer Trial Database for intraepithelial neoplasia