Cervix

Researchers in the Infections and Immunoepidemiology Branch (IIB) and the Clinical Epidemiology Unit (CEU), Clinical Genetics Branch, are leading priorities of the Cancer Moonshot. IIB is running the one-dose HPV vaccine trial in Costa Rica. CEU is creating new cervical cancer screening approaches that are effective and efficient. For high-resource settings, they are designing a quick and cost-effective HPV genotyping assay to improve the detection and management of cervical cancer.

ALTS is a study of the clinical management of low-grade cervical cytologic abnormalities conducted by the Clinical Genetics Branch and the NCI Division of Cancer Prevention.

A collaborative study on colposcopic biopsy with aims to study cervical disease on the lesion level, optimize criteria for biopsy placement, and analyze the incremental benefit of taking multiple biopsies

A study to evaluate a cohort of HIV-infected women using two novel and potentially sustainable, lower-cost tests for accurate screening for cervical cancer

The Enduring Guidelines Effort is a process to provide regular updates to the 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. A consensus committee reviews new evidence from population-based and other studies to continually improve clinical management.

A population-based natural history study of HPV and cervical neoplasia launched with Costa Rican colleagues in 1993.

This study, a Cancer Moonshot priority, is designed to develop a cervical cancer risk prediction model incorporating clinical and laboratory covariates. The goal is to classify women’s risks of cervical intraepithelial neoplasia 2 (CIN 2), CIN 3, and cancer into strata upon which clinical management decisions can be based. Eight articles comprising a supplemental issue in the Journal of Lower Genital Tract Disease formed the early core of this effort.

Human Papillomavirus (HPV) Cervical Visualization Study

The Costa Rica HPV Vaccine Trial (CVT) was a randomized, controlled phase III trial of the bivalent human papillomavirus-16/18 virus-like particle (VLP) vaccine. In addition to strong evidence for vaccine safety and efficacy, data from the trial demonstrated that three doses of the HPV vaccine may not be necessary, as similar vaccine efficacy against cervical HPV 16/18 infection was observed among women who received two, and even a single dose, after over 10 years of follow-up. At the completion of CVT in 2010, the CVT Long Term Follow-Up Study (LTFU) was implemented to extend the follow-up of CVT participants to 10 years, in order to address questions related to duration of protection, long-term safety, prolonged efficacy of fewer than three doses, and behavior of other carcinogenic HPV types in the absence of HPV 16/18 infections.

There is huge variability in risk of precancer and cancer conferred by different HPV types that is poorly explained. HPV type 16 is known to cause half of all cervical cancer cases worldwide, however, the specific reason for its carcinogenicity has been elusive. The HPV Genomics Project is designed to interrogate the relationship between sequence changes in the HPV genome and carcinogenicity.

A Cancer Moonshot priority to study methylation of the HPV viral genome and risk of cervical intraepithelial neoplasia 3+ to prevent cervical cancer

Studies of human papillomavirus (HPV) natural history, genomics and risk assessment that led to advances in screening and clinical management

The Persistence and Progression Cohort (PaP Cohort) is a collaborative study with Kaiser Permanente Northern California to create a repository of specimens for natural history studies, HPV typing, methylation, and HPV variant genomics.

IRIS is a comprehensive evaluation of candidate biomarkers for use in cervical cancer screening and triage in a large cohort study in partnership with Kaiser Permanente Northern California. This is a Cancer Moonshot priority.

The PRIMAVERA Immunobridging Trial was designed to provide convincing and actionable evidence that a single dose of the HPV vaccine will elicit an immune response sufficient to protect against targeted HPV infections and subsequent neoplasms. A single-dose schedule can potentially simplify vaccine delivery and vaccination program costs, which can ultimately ensure that more girls receive the vaccine.

The ESCUDDO Efficacy Trial is a scientific evaluation of one or two doses of the bivalent or nonavalent vaccine against human papillomavirus (HPV). Findings from the trial will provide the definitive evidence of the non-inferiority of one dose compared to two doses, the global gold standard in young girls. Positive results from the trial will provide actionable evidence needed to update the current HPV vaccine policy both domestically and globally.

The NCI is partnering with the George Washington University to evaluate novel biomarkers measured from self-collected samples in women undergoing cervical cancer screening. The Selfie Study is a Cancer Moonshot priority.

Researchers are conducting the PRISMA Efficacy trial to determine if one dose of HPV vaccine is sufficient to reduce the risk of HPV infection in women, compared to a non-HPV vaccine—the standard in the majority of the world. If one dose is sufficient, vaccinating women could help to accelerate the timeline for cervical cancer control, averting potentially millions of projected HPV-related cervical cancers expected over the coming decades as the population of the globe ages.

The NCI is partnering with the University of Mississippi Medical Center to evaluate risk of cervical precancer and to study novel biomarkers in women undergoing cervical cancer screening. STRIDES is a Cancer Moonshot priority.

A study to comprehensively assess biomarkers of risk for progressive cervical neoplasia, and thus develop a new set of biomarkers that can distinguish those at highest risk of cervical cancer from those with benign infection