Infections

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Immune System Diseases

Uterine Cervical Neoplasms

Communicable Diseases

Acquired Immunodeficiency Syndrome

HIV Infections

Papillomavirus Infections

Disease Attributes

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Virus Diseases

Genital Diseases

Urogenital Diseases

DNA Virus Infections

Tumor Virus Infections

HIV infected women between ages 18 - 64 years of age due for cervical cancer screening were enrolled.

Elizabeth A Stier, MD

The population of HIV infected women seen at Boston Medical Center may have a higher frequency of anal cytologic and histologic abnormalities than what is reported for the non-HIV infected population.

BACKROUND FOR THIS STUDY Anal cancer is a growing problem in the US. The incidence of anal cancer has increased among both men (160%) and women (78%) from 1973 to 2000 in the US \[1\]. In HIV-infected men the incidence of SCCA (squamous cell cancer of the anus) was found to range from 49-92 per 100,000 patient years \[2\]. This prompted recommendations on screening for anal cancer in this population. HIV-infected women are also at increased risk for developing anal cancer. A study based on data from AIDS and cancer registries found that the risk of anal cancer among women in the general population is about 1.2% and it increases up to 3.9% in the HIV-infected women. In addition, HIV-infected women had eight times the risk of in situ anal cancer compared with the number of expected cases \[3\].

SCCA appears to have many similarities to cervical cancers. HPV has been detected in 88% of anal cancer specimens with HPV-16 found in 73% of SCCA and HPV-18 in 7% \[1\]. In addition, SCCA develops in the transformation zone between the squamous epithelium of the anus and the columnar epithelium of the rectum, is frequently associated with dysplasia of the anus and may be preceded by squamous intraepithelial changes which are also associated with HPV.

Cervical cytology, also known as pap smear, can detect cervical cancer and its precursors. Countries who have adopted cervical cancer screening programs have had dramatic decreases in both the morbidity and mortality rates of cervical cancer.

Anal cytology may also be used to screen for HPV associated anal lesions, and among HIV-infected men who have sex with men, an abnormal cytology is frequently associated with a dysplastic squamous cell lesion of the anus. Anal HPV infections (high risk types) have been found in 53 ¿ 95% of HIV-infected men. Abnormal anal cytology has been found in 41-81% of HIV-infected men screened with high-grade cytologic findings in 2-25% of these patients \[2\].

There have been only a few studies looking at anal cytology in HIV-infected women. The largest study (n=235), by Holly and Palefsky \[4\], found that HIV positive women had a 26% prevalence of anal cytologic abnormalities (mostly atypical squamous cells of undetermined significance \[ASCUS\] and low grade squamous intraepithelial lesions \[LSIL\]). Forty-six of these women with abnormal cytology (60) underwent high resolution anoscopy (HRA) and 14 were found to have biopsy proven HSIL.

Several risk factors for anal cytologic abnormalities in women have been suggested, such as positive anal HPV test, history of anal intercourse, history of cervical squamous intraepithelial lesions (SIL), history of vulvar warts, multifocal cervical SIL, history of sexually transmitted infections, more than 10 sexual partners, history of cervical, vulvar or vaginal cancer, immunosuppression after solid organ transplantation, HIV infection, long-term corticosteroids use and cigarette smoking.

It has been suggested that all HIV-infected women, women with cervical cancer and women with high-grade vulvar disease or cancer should be screened for anal cytologic abnormalities. However, as described above there is very scanty literature describing the prevalence and incidence in this patient population and the largest study was conducted prior to the HAART era.

We plan to estimate the prevalence and 6-12 month incidence of abnormal anal cytology with histologic correlates in the HIV-infected women seen at BMC. We hope that the information will allow us to make screening recommendations for this patient population.

Anal HPV Infection and Abnormal Cytology in HIV-infected Women

Boston Medical Center

Attending and Associate Professor

Rare Diseases

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

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

Participant request physician assessment for Digital anal rectal exam, Anal cytology, Anal HPV test and High resolution anoscopy for every 6 months within 12 months period

Participant request physician assessment for Digital anal rectal exam, Anal cytology, Anal HPV test for every 6 months within 12 months period

Participant request physician assessment for Digital anal rectal exam, Anal cytology and High resolution anoscopy for every 6 months within 12 months period

Participant request physician assessment for Digital anal rectal exam, Anal cytology for every 6 months within 12 months period

Participant request physician assessment for Digital anal rectal exam, Anal HPV test and High resolution anoscopy for every 6 months within 12 months period

Participant request physician assessment for Digital anal rectal exam and Anal HPV test for every 6 months within 12 months period

Participant request physician assessment for Digital anal rectal exam and High resolution anoscopy for every 6 months within 12 months period

Participant request physician assessment for Digital anal rectal exam for every 6 months within 12 months period

Participant request Self-sampling collection for Anal cytology and Anal HPV test for every 6 months within 12 months period

Participant request Self-sampling collection for Anal cytology for every 6 months within 12 months period

Participant request Self-sampling collection for Anal HPV test for every 6 months within 12 months period

Participant request Self-sampling collection for Anal cytology and Anal HPV only at month 12

The goal of the optimization phase of MOST is to identify the most promising combination of experimental components in changing an outcome given a set of environmental constraints. Looking at effectiveness, efficiency, economy, and scalability criteria, we will focus on the proportion of anal HSIL identified (effectiveness), unit cost (efficiency and economy), and accumulating cost to the client over a 12-month period (economy). Meeting these criteria will likely imply scalability. The most appropriate anal HSIL screening algorithm would ideally be one which could

- identify anal HSIL in at least 20% of HIV-positive MSM and 10% of HIV-negative MSM at baseline and

OPTIMIZATION PHASE

Nittaya Phanuphak, MD,PhD.

Siriporn Nonenoy, RN.MPH.

Nittaya Phanuphak, MD.,Ph.D.

Napasawan Chinlaertworasiri

This the propose to use the Multiphase Optimization Strategy Trial (MOST) design to identify an anal HSIL screening algorithm which is most suitable in terms of effectiveness, efficiency, and economy. Specifically, The Investigators will use a factorial design as the main strategy in the MOST, as this allows the evaluation of multiple intervention components that are candidates for ultimate inclusion in the algorithm. The Investigators will then implement the most suitable anal HSIL screening algorithm in the clinic, using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework to guide its design, implementation, and evaluation. An interrupted time series will be used to compare anal HSIL screening uptake among men who have sex with men clients in the clinic, prior to and after the implementation of the new anal HSIL screening algorithm, and mixed-methods approaches will be used to evaluate components of the RE-AIM framework.

I. PREPARATION PHASE Purpose To lay groundwork for optimization of anal high-grade squamous intraepithelial lesion screening algorithm for MSM, and identify which test and component(s) should be included in the anal HSIL screening algorithm.

II. OPTIMIZATION PHASE Purpose To form an anal high-grade squamous intraepithelial lesion screening algorithm that meets the optimization criteria.

III. EVALUATION PHASE Purpose To establish whether the optimized anal high-grade squamous intraepithelial lesion screening algorithm has a statistically significant effect on service uptake among MSM compared to the standard of care.

Anal HSIL Screening Algorithm

Optimizing an Anal High-grade Squamous Intraepithelial Lesion Screening Algorithm for Thai Men Who Have Sex With Men and Transgender Women

identify anal HSIL in at least 20% of HIV-positive MSM/TGW and 10% of HIV-negative MSM/TGW within visit schedule.

Evaluate anal HSIL screening method uptake among MSM/TGW clients in the clinic compare to the implementation of the new anal HSIL screening method algorithm.

National Institutes of Health (NIH)

amfAR, The Foundation for AIDS Research

Institute of HIV Research and Innovation Foundation, Thailand

Digestive System Diseases

Papilloma

Anus Neoplasms

Anal Cancer

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Anal HPV Infection and Abnormal Cytology in HIV-infected Women	NCT00933140	Cervical Cancer... HIV Infections		18 Years - 64 Years	Boston Medical Center
Anal HSIL Screening Algorithm	NCT05531799	Anal High-grade...	OPTIMIZATION PH...	30 Years -	Institute of HIV Research and Innovation Foundation, Thailand
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
Anal HPV Infection and Abnormal Cytology in HIV-infected Women	NCT00933140	Cervical Cancer... HIV Infections		18 Years - 64 Years	Boston Medical Center
Anal HPV Infection and Abnormal Cytology in HIV-infected Women	NCT00933140	Cervical Cancer... HIV Infections		18 Years - 64 Years	Boston Medical Center
Anal HSIL Screening Algorithm	NCT05531799	Anal High-grade...	OPTIMIZATION PH...	30 Years -	Institute of HIV Research and Innovation Foundation, Thailand

Spots Global Cancer Trial Database for anal cytology