Detecting Anal and Genital Human Papillomavirus Infection and Squamous Intraepithelial Lesions in HIV-Positive Patients Enrolled in AIDS Cancer Clinical Trials

Study Overview
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Brief Summary
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RATIONALE: Diagnostic procedures, such as anal swab collection, digital rectal examination, and anal endoscopy and biopsy, may help find and diagnose anal and genital human papillomavirus infection and squamous intraepithelial lesions and help doctors plan better treatment. PURPOSE: This clinical trial is studying ways to detect anal and genital human papillomavirus infection and squamous intraepithelial lesions in HIV-positive patients enrolled in an AIDS cancer clinical trial.

Detailed Description
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OBJECTIVES: Primary To determine if various pharmacotherapeutic agents investigated in primary AIDS Malignancy Clinical Trials (AMC) for diseases other than human papillomavirus (HPV)-associated neoplasia have any preliminary evidence of activity against anogenital HPV infection or anogenital squamous intraepithelial lesions (ASIL) in HIV-positive patients participating in these trials. To describe changes in the types of anal HPV present and the prevalence of ASIL in patients treated on these studies. To evaluate cervical HPV infection and cervical/vulvovaginal disease in HIV-positive women participating in these trials. To describe changes in cervical HPV infection and cervical/vulvovaginal disease in these women after undergoing various study treatments. OUTLINE: This is a multicenter study. Patients undergo anal swab collection at baseline to obtain samples for anal cytology, anal human papillomavirus (HPV) typing, and other HPV-related testing (e.g., HPV viral load). Digital rectal examinations (DRE) are also performed as part of the baseline physical examination. Female patients also undergo cervical swab collection for cervical HPV testing and cytology, as well as colposcopy (if available) of the cervix and vulvovaginal region to completely assess lower genital tract HPV-related lesions. At sites where high-resolution anoscopy (HRA) is available, patients are encouraged, but not required, to have an HRA with biopsy of any visualized lesions within 30 days of collection of the swabs. After baseline assessments, patients undergo treatment with the investigative agent according to the study protocol requirements. If study treatment continues beyond 6 months, additional anal and cervical swabs are obtained for anal and cervical HPV and cytology along with DREs every 6 months until completion of study treatment and at the final study visit. Patients may also undergo additional HRA with biopsy and/or colposcopy of the lower genital tract with biopsy (women only) at this time. Patients with an abnormal anal cytology or histology are referred for HRA per local standard of care. If HRA is not available at the treatment site, patients undergo a DRE, and those with an abnormal DRE are referred for evaluation by a surgeon.

Official Title
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A Companion Protocol to Evaluate Anogenital Human Papillomavirus (HPV) Infection and Anogenital Squamous Intraepithelial Lesions (ASIL) in Subjects Participating in AMC Clinical Trials

Conditions
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Aids-related Malignancies, Lymphoma, Precancerous Condition, Sarcoma

Intervention / Treatment
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* Genetic: polymerase chain reaction
* Other: cytology specimen collection procedure
* Other: histological technique
* Procedure: colposcopic biopsy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Serologic documentation of HIV infection by any FDA-approved tests Enrolled in an AIDS Malignancy Clinical Trials Consortium (AMC) clinical trial of any new or existing pharmacotherapeutic agent for treatment of disease other than human papillomavirus (HPV)-associated neoplasia AMC study must have an accrual target of > 15 patients PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-1 OR Karnofsky PS 60-100% Life expectancy ≥ 3 months Not pregnant or nursing Patients receiving myelosuppressive therapy must meet the following criteria: ANC > 1,000/μL Platelet count > 50,000/μL Evaluated before treatment or completely recovered from their nadir Able to understand and willing to sign a written informed consent document No bleeding disorder or requirement for anticoagulation that would contraindicate any biopsy of the anal canal PRIOR CONCURRENT THERAPY: See Disease Characteristics

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Specimen Collection<br>Blood collection, anal cytology and biopsy of observed lesions. Additional cervical cytology and biopsy for females. | Genetic: polymerase chain reaction<br>* PCR for HPV DNA detection, performed on specimens collected at baseline, every 6 months while on parent protocol, treatment discontinuation on parent protocol, final visit on parent protocol.<br>Other: cytology specimen collection procedure<br>* Detection of HPV-associated neoplasia at baseline, every 6 months while on parent protocol, treatment discontinuation on parent protocol, final visit on parent protocol.<br>Other: histological technique<br>* Detection of HPV-associated neoplasia at baseline, treatment discontinuation on parent protocol, final visit on parent protocol.<br>Procedure: colposcopic biopsy<br>* Where observed during HRA, collection of tissue for detection of HPV-associated neoplasia at baseline, treatment discontinuation on parent protocol, final visit on parent protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activity of pharmacotherapeutic agents being investigated in AIDS Malignancy Clinical Trials (AMC) against anogenital human papillomavirus (HPV) infection or anogenital squamous intraepithelial lesions (ASIL) |  | Baseline, every 6 months while on parent protocol, treatment discontinuation on parent protocol, final visit on parent protocol | 
| Cervical HPV infection and cervical/vulvovaginal disease in women participating in AMC clinical trials |  | Baseline, every 6 months while on parent protocol, treatment discontinuation on parent protocol, final visit on parent protocol | 
| Changes in cervical HPV infection and cervical/vulvovaginal disease after treatment on AMC studies |  | Baseline, every 6 months while on parent protocol, treatment discontinuation on parent protocol, final visit on parent protocol | 
| Changes in anal HPV types present |  | Baseline, every 6 months while on parent protocol, treatment discontinuation on parent protocol, final visit on parent protocol | 
| Frequency of ASIL |  | Baseline, treatment discontinuation on parent protocol, final visit on parent protocol | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV Infections, high-grade squamous intraepithelial lesion, low-grade squamous intraepithelial lesion, human papilloma virus infection, AIDS-related diffuse large cell lymphoma, AIDS-related diffuse mixed cell lymphoma, AIDS-related diffuse small cleaved cell lymphoma, AIDS-related immunoblastic large cell lymphoma, AIDS-related Kaposi sarcoma, AIDS-related lymphoblastic lymphoma, AIDS-related malignancies, AIDS-related peripheral/systemic lymphoma, AIDS-related primary CNS lymphoma, AIDS-related small noncleaved cell lymphoma, multicentric Castleman disease