Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Infections

Immune System Diseases

Symptoms and General Pathology

Uterine Cervical Neoplasms

Carcinoma

Papilloma

Acquired Immunodeficiency Syndrome

HIV Infections

Immunologic Deficiency Syndromes

Virus Diseases

Syndrome

Communicable Diseases

Urogenital Diseases

Genital Diseases

Blood-Borne Infections

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Lentivirus Infections

Retroviridae Infections

RNA Virus Infections

Slow Virus Diseases

Neoplasms, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

All Drugs and Chemicals

Vaccines

Blood collection

Oral, cervicovaginal and anal specimen collection at enrollment and follow-up visits

Oral, cervicovaginal and anal specimen collection

Used for management in follow-up visits of persistent anal HPV16/18+ in WLWH

Anoscopy & Biopsy of Acetowhite Lesions

Used for management in follow-up visits of persistent type-specific high-risk HPV cervicovaginal HPV

Colposcopy & Biopsy of Acetowhite Lesions

Use for management in follow-up visits of persistent cervicovaginal HPV 16/18+ in WLWH, as identified in colposcopy and biopsy

Ablative Treatment

Use for management in follow-up visits of persistent cervicovaginal HPV 16/18+ in WLWH, as identified in colposcopy and biopsy that ablation ineligible

LEEP (Loop Electrosurgical Excision Procedure)

Kathryn A Anastos, MD

Philip E Castle, PhD, MPH

Gad Murenzi, MD, MPH

Our study will assess and measure population effectiveness of prophylactic HPV vaccine in reducing cervical, anal, and/or oral prevalent and 6-month persistent infections among HPV-vaccinated and 757 HPV-unvaccinated Rwandan WLWH aged 18-26 years. Additional objectives include the quantification \& examination of long-term antibody (into young adulthood) responses to HPV vaccination and to validate the performance (e.g., sensitivity and specificity) of a low-cost, POC (point-of-care) anti-HPV16 antibody test to determine/confirm HPV vaccination status. The findings for this study will provide necessary evidence regarding the long-term protection afforded by HPV vaccination in WLWH living in SSA, who are at the greatest risk of HPV-related cancers.

Cervical cancer is the 4th most common cancer and cause of cancer-related death in women globally; in many lower-resource settings, especially sub-Saharan Africa (SSA), it is the most common. Virtually all cervical cancer and precancer are caused by 12-15 high-risk human papillomavirus (HPV) types. HPV16 causes approximately 55-60% and HPV18 causes approximately 10-15% of cervical cancer while the remaining 12 HPV types cause the remaining 25-30% of cervical cancer. High-risk HPV, predominately HPV16, also causes most anal, vulvar, vaginal, and penile cancers and a significant proportion of oropharyngeal cancers. Prophylactic HPV vaccines have been developed and have been shown to be nearly 100% protective against incident HPV infection and related abnormalities in the general population. However, the evidence for the effectiveness of prophylactic HPV vaccines in women living with human immunodeficiency virus (HIV) (WLWH) is less clear. HIV infection increases the risk of cervical cancer due to an impaired immune response to HPV.

Rwanda is a high-burden cervical cancer country where the prevalence of HIV is 3.7% among adult women, with higher HIV prevalence among young women (1). In 2011, Rwanda implemented a national HPV vaccination program with Gardasil®, which protects against HPV16 and HPV18, the two HPV types that cause \~70% of cervical cancer, and HPV6 and HPV11, the two types that cause \~90% of anogenital warts (HPV6/11/16/18). Their program has achieved \>90% coverage of the target population, primarily girls aged 12 years, annually. The implementation of a highly successful HPV vaccination program and the high prevalence of HIV, in addition to the research and medical capacity that Albert Einstein College of Medicine (Einstein) has helped to build at the Rwanda Military Hospital (RMH) and University of Rwanda (UR), makes Rwanda the ideal locale to study the long-term effects of HPV vaccination in WLWH.

To answer questions about HPV vaccine effectiveness and immunity in Rwandan WLWH, collaborators at Einstein, RMH, and UR will conduct an observational study of WLWH and HIV-negative (HIV\[-\]) women who did (birth cohorts 1997 and later) and WLWH who did not (birth cohorts before 1997) receive HPV vaccination through the national vaccination program. The investigators will compare cervicovaginal, anal, and oral prevalent and 6-month persistent HPV6/11/16/18 infections in 757 HPV-vaccinated WLWH to those in 757 unvaccinated WLWH and 757 HPV-vaccinated HIV\[-\] women. The investigators will also compare the HPV immune response in 548 HPV-vaccinated WLWH to 548 HPV-vaccinated HIV\[-\] women and the impact of switching from 3 doses to 2 doses of Gardasil® in 2015. Finally, the investigators will investigate the risk factors, including the cervicovaginal microbiome, for prevalent and 6-month persistent HPV infection in young WLWH and HIV\[-\] women. The long-term goal is to establish a cohort of WLWH in whom we can examine the long-term effectiveness of HPV vaccination in WLWH now and in the future. This contribution is significant as it will establish the population effectiveness of HPV vaccination in WLWH living in SSA, the group of women at the highest risk of cervical cancer, for which there is a dearth of evidence. The proposed research is innovative as it leverages and expands the local research and medical capacity in Rwanda to examine one of the critically unanswered questions about HPV vaccine effectiveness in the context of the World Health Organization's (WHO) call for the elimination of cervical cancer.

De-identified pictures of participants' cervix, blood collection, oral swab specimen, cervical swab specimen and anal swab specimen

HPV Vaccine Effectiveness Study in Rwandan Women Living With HIV

Long-Term Human Papillomavirus Vaccination Effectiveness and Immunity in Rwandan Women Living With and Without Human Immunodeficiency Virus

To measure population effectiveness of prophylactic HPV vaccine in reducing cervicovaginal, anal, and/or oral prevalent and 6-month persistent infections by HPV6/11/16/18

To quantify, and examine the determinants of, long-term antibody (into young adulthood) responses to HPV vaccination

Conduct a natural history study to investigate determinants, including cervicovaginal microbiome (CVM), of short-term HPV persistence in young WLWH and HIV\[-\] women living in a SSA setting

National Cancer Institute (NCI)

Rwanda Military Hospital

University of Rwanda

Montefiore Medical Center

Rare Diseases

Squamous Intraepithelial Lesions of the Cervix

Uterine Cervical Dysplasia

Precancerous Conditions

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Cervical Intraepithelial Neoplasia

Patients diagnosed with Low-Grade Squamous Intraepithelial Lesions that were managed with observation and evaluation at 6 and 12 months after diagnosis.

Patients diagnosed with Low-Grade Squamous Intraepithelial Lesions that were managed with an ablative treatment and evaluated at 6 and 12 months after diagnosis.

Use of an ablative treatment (cryotherapy) for the management of Low-Grade Squamous Intraepithelial Lesions of the cervix.

Ablative treatment

Patients diagnosed with Low-Grade Squamous Intraepithelial Lesions were managed with observation and evaluation at 6 and 12 months after diagnosis.

Expectant management

Osvaldo Reyes, MD

To evaluate the rate of regression and progression of low-grade squamous intraepithelial lesion comparing expectant vs. ablative treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
HPV Vaccine Effectiveness Study in Rwandan Women Living With HIV	NCT05247853	Cervical Cancer Human Papilloma... Human Immunodef... HPV-Related Car...	Blood collectio... Oral, cervicova... Anoscopy & Biop... Colposcopy & Bi... Ablative Treatm... LEEP (Loop Elec...	18 Years - 28 Years	Montefiore Medical Center
Observational vs. Ablative Treatment for Low-grade Squamous Intraepithelial Lesions.	NCT02331550	LSIL, Low-Grade...	Ablative treatm... Expectant manag...	-	Saint Thomas Hospital, Panama
Observational vs. Ablative Treatment for Low-grade Squamous Intraepithelial Lesions.	NCT02331550	LSIL, Low-Grade...	Ablative treatm... Expectant manag...	-	Saint Thomas Hospital, Panama

Spots Global Cancer Trial Database for ablative treatment