Infections

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

All Conditions

Neoplasms

Rare Diseases

Acquired Immunodeficiency Syndrome

HIV Infections

Squamous Intraepithelial Lesions of the Cervix

Carcinoma

Carcinoma, Squamous Cell

Carcinoma in Situ

Uterine Cervical Dysplasia

Precancerous Conditions

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Cervical Intraepithelial Neoplasia

Anti-Infective Agents

All Drugs and Chemicals

Micronutrients

Coagulants

Proflavine

Iodine

Lugol's solution

Cadexomer iodine

Anti-Infective Agents, Local

5-10 ml of proflavine hemisulfate (0.01%) will be applied on the anal epithelium. The mHRME will then be inserted and imaging of abnormal tissues will be performed.

This is a single-arm study where all subjects will receive both standard of care HRA (High resolution anoscopy) and experimental mHRME imaging.

Standard of care (SOC) high-resolution anoscopy (HRA) with Lugol's iodine will be performed. The unstained (abnormal) area will be evaluated with mHRME for optical biopsy diagnosis:

1. contrast agent will be applied to anal epithelium (5-10 ml of proflavine hemisulfate (0.01%)),
2. the mHRME will then be inserted and imaging of abnormal tissues will be performed. This will add 2 to 6 minutes per procedure.

This is a single-arm study where all subjects will receive both SOC HRA and experimental mHRME imaging.

mHRME (Mobile High resolution microendoscope)

Contrast agent will be applied to anal epithelium (5-10 ml of proflavine hemisulfate (0.01%)) to use with the mHRME

Proflavine Hemisulfate

Standard of care (SOC) HRA with Lugol's iodine will be performed.

High resolution anoscopy

Sharmilla Anandasabapathy, MD

Elizabeth Y Chiao, MD

The investigators have developed a portable, battery-operated, mobile high-resolution microendoscope (mHRME) that provides subcellular images of the anal epithelium, delineating the cellular and morphologic changes associated with neoplasia. The investigators' central hypothesis is that this 'optical' approach will increase the efficiency, clinical impact, and cost-effectiveness of the current standard of high-resolution anoscopy(HRA)-guided biopsy, thus facilitating usage by less-experienced clinicians in community-based or low-resource settings. To validate this, the investigators will conduct a study to determine the efficiency and diagnostic characteristics of the mHRME 'optical biopsy' approach versus the current standard of HRA-based tissue biopsy. Successful results will allow for improved efficacy and resource utilization for cancer screening in people living with HIV for anal cancer and other epithelial cancers including the cervix, oral cavity, bladder, and GI tract.

The investigators' central hypothesis is that using mHRME plus three-dimensional (3D) mapping as a diagnostic tool will improve the accuracy and efficiency of HSIL diagnoses. Additionally, the investigators hypothesize that the sensitivity (SN) specificity (SP), positive predictive value (PPV), and negative predictive value (NPV), as well as the receiver operating characteristic (ROC) curve for the identification of neoplasia on a per biopsy and per patient basis will be high. The investigators will first compare the HRA-directed biopsy (as the gold standard) to the results of the mHRME HSIL diagnosis. The SN of mHRME diagnosis in the detection of HSIL will be estimated with the binomial proportion of study participants who are positive for HSIL on HRA-guided biopsy at two thresholds of histology thresholds which are: 1) Anal intraepithelial neoplasia (AIN) 2+ threshold, and 2) AIN3+ threshold. SP will be estimated as the proportion of study participants who are negative for HSIL on HRA-guided biopsy at both thresholds. PPV and NPV will be estimated using the binomial proportion and 95% confidence interval (CI). In addition, Cohen's kappa statistic and ROC curves will be generated if patient characteristics such as low Clusters of differentiation 4 (CD4) count, combined antiretroviral treatment (cART) utilization, or high HIV viral load impact the determination of SN and SP. SN and SP of mHRME-based HSIL diagnosis will be estimated on a per lesion and per patient basis with 95% CI and compared by McNemar's test. A generalized linear model for logistic regression with multiple correlated outcomes will compare SN and SP of each method on a per biopsy and per patient basis.

Primary Objective:

To determine if the mHRME plus 3D mapping improves the accuracy of anal HSIL diagnosis compared to the gold standard of histologic diagnosis of HSIL by HRA-guided biopsy.

Secondary Objectives:

Determination whether HRME changes the decision to perform biopsy.

This is a single-arm study where all subjects will receive both standard of care HRA (High resolution anoscopy) and experimental mHRME imaging.

The Effectiveness of High Resolution Microendoscopy for People Living With HIV

The Effectiveness of High Resolution Microendoscopy (HRME) in High Grade Intraepithelial Lesions (HSIL) Diagnosis for People Living With HIV

The primary outcome of this study is to measure the operating characteristics including SN, SP, PPV and NPV comparing the physician- and algorithm- guided HRME-based image compared to the Lugol's- guided physician diagnosis of HSIL during HRA. Gold standard consensus pathology was used and pathology data needs to be obtained, verified, and entered.

Diagnostic yield: The number of neoplastic biopsies/total number of biopsies obtained in patients who received biopsies.

Total procedure time (HRA+HRME+biopsies) vs HRME time alone

Icahn School of Medicine at Mount Sinai

William Marsh Rice University

University of California, San Francisco

The University of Texas Health Science Center, Houston

M.D. Anderson Cancer Center

Medical University of South Carolina

Baylor College of Medicine

Professor of Medicine

Digestive System Diseases

Anus Neoplasms

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Anus Diseases

Rectal Diseases

Anal Cancer

Antineoplastic Agents

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive nivolumab while on study. Patients undergo sigmoidoscopy, colonoscopy or anoscopy, proctoscopy or digital rectal exam, x-ray, CT scan, MRI, biopsy and blood sample collection throughout the study.

Patients undergo observation while on study. Patients undergo sigmoidoscopy, colonoscopy or anoscopy, proctoscopy or digital rectal exam, x-ray, CT scan, MRI, biopsy and blood sample collection throughout the study.

Biopsy

Biospecimen Collection

Colonoscopy

Computed Tomography

Digital Rectal Examination

High Resolution Anoscopy

Magnetic Resonance Imaging

Patient Observation

Proctoscopy

Sigmoidoscopy

X-Ray Imaging

Lakshmi Rajdev

This phase III trial investigates how well nivolumab after combined modality therapy works in treating patients with high risk stage II-IIIB anal cancer. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVE:

I. To evaluate whether therapy with nivolumab following combined modality therapy (CMT) improves disease-free survival (DFS) compared with observation in patients with high risk anal carcinoma.

SECONDARY OBJECTIVES:

I. To compare nivolumab following combined modality therapy (CMT) with observation in patients with high risk anal carcinoma with regard to:

Ia. Objective response rate (complete \[CR\] and partial \[PR\]), stable disease and progression.

Ib. Severe toxicity interval. Ic. Colostomy-free survival. Id. Overall survival. Ie. Toxicity.

OUTLINE: Patients who received standard CMT are randomized to 1 of 2 arms.

ARM A: Patients receive nivolumab intravenously (IV) while on study.

ARM B: Patients undergo observation while on study

Patients undergo sigmoidoscopy, colonoscopy or anoscopy, proctoscopy or digital rectal exam, x-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI), biopsy and blood sample collection throughout the study.

Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer

A Randomized Phase III Study of Nivolumab After Combined Modality Therapy (CMT) in High Risk Anal Cancer

Will be defined as the occurrence of progression of local disease, distant metastases, second primary or death from the date of randomization.

Will be defined by complete and partial response.

The following late side effects are considered as severe: any anal/rectal damage (ulcer, fistula, or perforation), rectal stenosis that required colostomy, skin ulceration, and severe fibrosis. This parameter estimates the probability of being free of late side effects for patients under loco-regional control.

Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Canadian Cancer Trials Group

National Cancer Institute (NCI)

Virus Diseases

Papilloma

Standard of care anal cancer screening with anal cytology, HPV testing and high resolution anoscopy.

The initial screening interventions will include the collection of (1) anal cytology; (2) self-collected HPV testing specimens (by subjects); (3) a clinician collected HPV specimen. A digital rectal exam will also be done on all patients.

Diagnostic tests for anal cancer screening

Daniela Solis

Nadia M Zubair, MPH

Keith Sigel, MD PHD MPH

Ashish Deshmukh, PhD

Elizabeth Chiao

Elizabeth Chiao, MD

Keith Sigel, MD, PhD, MPH

The goal of this single arm trial is to prospectively evaluate screening methods for anal cancer precursors in HIV uninfected women with a history of lower genital tract neoplasias and cancers.

This single arm trial will enroll 300 HIV uninfected women with a history of genital neoplasia (ie., cervical intraepithelial neoplasia grade 2-3, vaginal intraepithelial neoplasia grade 2-3 or vulvar intraepithelial neoplasia grade 2-3) or early stage cervical or vulvar cancer to evaluate the test characteristics of anal cancer screening tests (cytology, HPV testing and high resolution anoscopy) and determine the prevalence and incidence of anal high-grade squamous intraepithelial lesions in this population. Participants will undergo evaluation at baseline and then at 12 and 24 months. The investigators will also measure the acceptability of anal cancer screening in this previously unstudied group. The trial is expected to run from 2021-2025.

Screening Women With Prior HPV for Anal Neoplasia

The Effectiveness of Screening Women With Lower Genital Tract Neoplasia or Cancers for Anal Cancer Precursors

All of the individual participant data collected during the trial, after deidentification.

Proportionate concordance of high-risk HPV testing

Proportion of subjects with high-risk HPV and subtype proportions

Proportion of subjects with new aHSIL during follow-up period

Survey measures anal cancer screening test acceptability. Each item is scored 0-3, with higher score indicting more acceptability. 0-3. There is no total scale. Each question is scored separately and the overall results are used qualitatively.

Proportion of subjects with new hrHPV infection

Proportion of subjects with prevalent hrHPV without measurable hrHPV at follow-up

Associate Professor

Symptoms and General Pathology

Communicable Diseases

Papillomavirus Infections

HIV Seropositivity

Disease Attributes

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

DNA Virus Infections

Tumor Virus Infections

* Standard proctologic examination with digital rectal examination and 2 anal swabs at initial inclusion visit, Month 12 and Month 24 follow-up visits and if applicable Month 6 and Month 18 control visits
* High resolution anoscopy at initial inclusion visit, Month 12 and Month 24 follow-up visits and if applicable Month 6 and Month 18 control visits
* Biopsy(ies) during High Resolution Anoscopy only if lesion suggestive of AIN detected during High Resolution Anoscopy
* High Resolution Anoscopy biannually only if high-grade lesion (ASC-H, HSIL ou AIN2/3)

(with digital rectal examination and 2 anal swabs) at initial inclusion visit, M12 and M24 follow-up visits and if applicable M6 and M18 control visits

Standard proctologic examination

at initial inclusion visit, Month 12 and Month 24 follow-up visits and if applicable Month 6 and Month 18 control visits

only if lesion suggestive of AIN detected during High Resolution Anoscopy

Biopsy(ies) during High Resolution Anoscopy

Only if high-grade lesion (ASC-H, HSIL ou AIN2/3)

High Resolution Anoscopy biannually

Isabelle Etienney

Gary Clifford

Multicentric epidemiological non-comparative study in France characterising evolution of anal Human papillomavirus (HPV) infection and related lesions and evaluating markers associated with the observed evolution.

Estimated enrolment: 500

Principal Outcomes

* Detection of high-grade cytological and histological anal lesions by high resolution anoscopy
* Spontaneous regression of high-grade anal lesions
* Detection of anal HPV infection

Intervention (procedure):

* Patient medical interview (initial inclusion visit, Month 12 and Month 24 follow-up visits and if applicable Month 6 and Month 18 control visits)
* Standard proctologic examination with digital rectal examination and 2 anal swabs (initial inclusion visit, Month 12 and Month 24 follow-up visits and if applicable Month 6 and Month 18 control visits)
* High resolution anoscopy (initial inclusion visit, Month 12 and Month 24 follow-up visits and if applicable Month 6 and Month 18 control visits)

Only if lesion suggestive of Anal Intraepithelial Neoplasia (AIN) detected during High Resolution Anoscopy (HRA):

- anal biopsy(ies) during HRA

Only if high-grade lesion:

- HRA biannually

Intervention (procedure):

* Patient medical interview (initial inclusion visit, Month 12 and Month 24 follow-up visits and if applicable Month 6 and Month 18 control visits)
* Standard proctologic examination with digital rectal examination and 2 anal swabs (initial inclusion visit, Month 12 and Month 24 follow-up visits and if applicable Month 6 and Month 18 control visits)
* High resolution anoscopy (initial inclusion visit, Month 12 and Month 24 follow-up visits and if applicable Month 6 and Month 18 control visits)

Only if lesion suggestive of Anal Intraepithelial Neoplasia (AIN) detected during High Resolution Anoscopy (HRA):

- anal biopsy(ies) during HRA

Only if high-grade lesion (Atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H), High grade Superficial Intra-epithelial Lesion (HSIL) or AIN2/3):

- HRA biannually

Human Papillomavirus Infection and Related Anal Lesions in HIV-positive Men Who Have Sex With Men

Natural History of Anal Human Papillomavirus Infection and Associated Disease in HIV-infected Men Who Have Sex With Men: Towards an Evidence Base for the Prevention of Anal Cancer.

ANRS, Emerging Infectious Diseases

Diseases and Abnormalities at or Before Birth

Congenital Abnormalities

Therefore, it is proposed we conduct a longitudinal study of the epidemiology of low risk and high risk HPV infection and related low grade and high grade anal cancers in HIV negative and HIV positive homosexual men who are 35 years or older. Participants are asked questions about recent experiences of anal intercourse in the last six months.

At baseline, all men (both HIV positive and HIV negative)will undergo a behavioural questionnaire, and anal swabs which will be tested for HPV and cytology. An HRA will also be performed on all men. Blood will be collected for HIV testing for HIV negative participants, syphilis and storage. Participants will be followed up for three years with one six-monthly visit in the first year then annually. A 6th study visit to discuss all study results will take place 2-3 months after the 5th study visit. A behavioural questionnaire, an anal swab, and HRA will be administered at all follow up interviews.

Participants asked questions about recent experiences of anal intercourse in the last six months.

The HRA is performed on HIV positive and HIV negative participants by study doctor after an examination of the perianal region and perineum. The plastic anoscope is inserted into the anal canal and visualised under high resolution magnification. Biopsy samples will be taken by the clinician for histological assessment if there are any detected abnormalities.

Carmella Law, MBBS; FAChSHM;

David Templeton, MBChB; PhD;

SPANC stands for Study of the Prevention of Anal Cancer. There are more than 100 types of human papillomavirus (HPV). Some HPV types cause genital warts and other types cause more than 90% of anal cancer.

Gay men are over 20 times more likely than others to develop anal cancer.

SPANC is a study of anal (HPV) infection and related anal disease in gay men. The study will provide important information to guide the possible future introduction of anal cancer screening programs for gay men.

Study title: The natural history of anal human papillomavirus (HPV) infection and anal cellular abnormalities in homosexual men.

Protocol version: 7, dated 1 September 2013. Approved by Ethics Committee on 24th October, 2013

Objectives: Among homosexual men aged 35 years or above to determine:

1. Prevalence, incidence and risk factors for specific types of HPV infection.
2. Prevalence, incidence and risk factors for histologically confirmed anal low grade and high grade squamous intraepithelial lesions (LSIL and HSIL).
3. Type-specific rates of clearance and persistence of anal HPV infection.
4. Rates of disease progression, regression and predictors in the spectrum of anal dysplasia.
5. Psychosocial/quality of life impact of anal cytology screening in homosexual men.

Study results will be used to inform possible development of guidelines for carrying out an anal cancer screening program in this population.

The study design is a prospective longitudinal design. Upon enrolment, participants will be followed up for three years to allow the study of both prevalence and incidence of HPV infection and related conditions.

Planned sample size: 600 homosexual men will be screened and enrolled from community based settings in Sydney, Australia.

The inclusion criteria are:

* male homosexual aged 35 years or above;
* HIV positive participants: documented to be HIV positive;
* HIV negative participants: tested HIV negative at recruitment; provision of informed, written consent.

The exclusion criteria are:

* participants unable to attend scheduled follow-up interviews or unwilling to undergo high resolution anoscopies (HRA);
* unable to understand English;
* having bleeding disorders or currently taking anti-anticoagulant medications; \*having previously received HRA;
* having ever been diagnosed with anal cancer.

Study procedures:

* At baseline, all men will undergo a behavioural questionnaire, and anal swabs which will be tested for HPV and cytology.
* An HRA will also be performed on all men.
* Blood will be collected for HIV testing for HIV negative participants, syphilis and storage. Participants will be followed up for three years with one six-monthly visits in the first year and then annually. A 6th study visit to discuss all study results will take place 2-3 months after the 5th study visit. A behavioural questionnaire, blood collection (except at six month); an anal swab and HRA will be administered at all follow up interviews.

The SPANC study is a prospective cohort study of the national history of anal human papillomavirus (HPV) infection and anal cellular abnormalities in homosexual men aged 35 years and above in Sydney. It is expected that the study results will be influential in the possible development of an anal cancer screening program in high-risk populations. Data on the natural history of anal HPV infection in homosexual men recruited from community-based settings are rare. We aim to recruit a total of 600 men, 360 HIV-negative and 240 HIV-positive. This will make the SPANC study one of the biggest ongoing anal HPV natural history study in the world to provide critical data on the incidence and clearance of anal HPV infection, progression and regression of pre-cancerous HPV associated anal lesions, the potential psychological impact on men who participate anal cancer screening programs, and the cost-effectiveness of rolling out these programs.

Statistical considerations: Sample size calculation: Assuming the incidence of HSIL is 5 and 15 per cent 100 person-years in HIV negative and HIV positive men, respectively, the 95% confidence intervals will be 4.2-6.0 in the HIV negative arm and 12.6-17.8 per 100 person-years in the HIV positive arm. Analysis plan: HPV prevalence and incidence, including overall, low risk, high risk and individual types, will be calculated according to participant's HIV status. Prevalence and incidence of LSIL and HISL will be calculated in the same fashion. Clearance and persistence of HPV infection, and progression and regression of HSIL will also be determined. Risk factors for prevalent HPV infection and LSIL and HSIL will be analysed using logistical regression. Risk factors for incident conditions will be analysed using Cox regression.

Duration of the study: The study will take place from 13/September/2010 to 21/Dec/2018. Participants will be recruited from 2010 to 2015 and followed up for three years.

Study of the Prevention of Anal Cancer

The Natural History of Anal Human Papillomavirus Infection and Anal Cellular Abnormalities in Homosexual Men

Aims to determine the prevalence, incidence and risk factors for type-specific HPV (37 types)

To determine if HPV is associated with LSIL and HSIL

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Effectiveness of High Resolution Microendoscopy for People Living With HIV	NCT04563754	Anal High Grade...	mHRME (Mobile H... Proflavine Hemi... High resolution...	18 Years -	Baylor College of Medicine
Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer	NCT03233711	Anal Basaloid S... Anal Canal Cloa... Anal Margin Squ... Stage IIB Anal ... Stage III Anal ...	Biopsy Biospecimen Col... Colonoscopy Computed Tomogr... Digital Rectal ... High Resolution... Magnetic Resona... Nivolumab Patient Observa... Proctoscopy Sigmoidoscopy X-Ray Imaging	18 Years -	National Cancer Institute (NCI)
Screening Women With Prior HPV for Anal Neoplasia	NCT05217940	HPV-related Low... HPV-related Ana... Early Stage Low...	Diagnostic test...	35 Years -	Icahn School of Medicine at Mount Sinai
Screening Women With Prior HPV for Anal Neoplasia	NCT05217940	HPV-related Low... HPV-related Ana... Early Stage Low...	Diagnostic test...	35 Years -	Icahn School of Medicine at Mount Sinai
Human Papillomavirus Infection and Related Anal Lesions in HIV-positive Men Who Have Sex With Men	NCT02287961	Hiv Infection	Standard procto... High resolution... Biopsy(ies) dur... High Resolution...	35 Years - 80 Years	ANRS, Emerging Infectious Diseases
Study of the Prevention of Anal Cancer	NCT02007421	Human Papilloma... Cancer	Participants as... High Resolution...	35 Years -	Kirby Institute
The Effectiveness of High Resolution Microendoscopy for People Living With HIV	NCT04563754	Anal High Grade...	mHRME (Mobile H... Proflavine Hemi... High resolution...	18 Years -	Baylor College of Medicine
Human Papillomavirus Infection and Related Anal Lesions in HIV-positive Men Who Have Sex With Men	NCT02287961	Hiv Infection	Standard procto... High resolution... Biopsy(ies) dur... High Resolution...	35 Years - 80 Years	ANRS, Emerging Infectious Diseases

Spots Global Cancer Trial Database for high resolution anoscopy