The Ovarian Cancer Observatory: Prevention, Impact, and Learning from Opportunistic Salpingectomy
Abstract
The vast majority of ovarian cancers are epithelial in origin. These are not a single disease, but rather five distinct diseases (referred to as histotypes). These five histotypes, in order of frequency, are high-grade serous (HGSC), endometrioid (ENOC), clear cell (CCOC), low-grade serous (LGSC), and mucinous ovarian cancer. The ovary is frequently the site of the dominant tumor mass when these cancers present, which led to the belief that ovarian cancer arises from transformation of the ovarian surface cells. However, in the past 20 years, it has become apparent that many HGSCs (the most common and lethal histotype) arise in the fallopian tube. The origin of each histotype of ovarian cancer remains an area of active debate and is important to understand to inform prevention, diagnostics, and treatment of each histotype. The recognition that the fallopian tube is where many HGSCs originate has led to an important prevention strategy, removal of the fallopian tubes during other pelvic surgeries. Opportunistic salpingectomy (OS) collectively refers to the removal of fallopian tubes (salpingectomy) during the time of other common surgical procedures (opportunistic), in particular at hysterectomy (removal of the uterus) or instead of tubal ligation (tying tubes) for sterilization. OS is now recommended practice in at least nine different countries. Research has shown that it is safe, feasible, and cost-effective. Recent data from British Columbia (BC), Canada, has also shown that it is likely effective in preventing HGSCs. There has not been a single case of HGSC following OS in BC, where it has been commonly performed since 2008. This is significantly fewer than were expected if cancers were arising at the same rate in the OS group as in the control group (people who had hysterectomy alone or tubal ligation), where there were 15 cases of HGSC. While no evidence to date has directly addressed whether OS reduces risk for ENOC and CCOC (the two next most common histotypes), we hypothesize that it will be at least partially effective in preventing many of these cancers as well. This is because these forms of cancer are believed to originate in the uterus and reach the ovary through the fallopian tube, which is supported by evidence showing that tubal ligation (tying tubes) decreases ENOC risk by 52% and CCOC risk by 48%. Herein, we propose to create the Ovarian Cancer Observatory, which will track the impact of OS and use this unique opportunity to better understand the origins of ovarian cancer. We will do this by using large, population-based datasets, as well as by generating new case-based data through a broad-based international collaboration to answer important questions about the etiology of different histotypes of ovarian cancer. We will examine whether ovarian cancers differ qualitatively when they arise following fallopian tube removal than when they arise in people with fallopian tubes. We hypothesize that OS will preferentially prevent specific histotypes of ovarian cancer (i.e., those that arise or travel through the fallopian tubes). We also hypothesize that HGSCs that arise following OS will be genomically and molecularly distinct from those that arise in people with intact fallopian tubes. To test this hypothesis, we propose two aims: Aim 1. Determine whether and by how much OS reduces the incidence of HGSC, ENOC and CCOC. Aim 2. Determine whether ovarian carcinoma cases occurring post-OS are qualitatively distinct from control cases of the same histotype. We will work with the population-based administrative datasets in the Canadian provinces of BC and Ontario to generate effectiveness data on OS for HGSC, ENOC, and CCOC. These data on an underlying population of 20 million people will be large enough to assess the incidence of each of these histotypes following OS. We have also engaged an international network of pathologist researchers from large volume hospitals/cancer c
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310957
Entities
People
- Gillian Hanley
Organizations
- United States Army
- University of British Columbia