Origins of cancer: from the cervix to the fallopian tube

Abstract

Success in cancer prevention depends on our understanding of its origins. In the past several years, we have gained insights into the pathogenesis of both cervical and ovarian cancer. We have identified a unique cell at the cervical squamo-columnar junction that has been proposed as a potential origin for most cervical cancers. This new information has put cervical precursors into perspective and explained the diversity of phenotypes associated with high-risk HPV infections. Moreover, it has raised the intriguing possibility that the squamo-columnar junction could be targeted in a cervical cancer prevention strategy for women who would not gain the maximum benefit from vaccination. In the upper genital tract, another unique precursor sequence has been identified in the distal fallopian tube, an indirect benefit from pathologic protocols that target the fimbria (SEE-FIM) for careful examination. Such studies have revealed the fimbria to be a starting point for high-grade serous carcinomas. By anchoring the origin of a high percentage of these tumors in the fimbria rather than ovary, investigators can now explore the exceptions to this new 'rule' and whether a dualistic model of high-grade serous cancer exists. These endeavors have placed the pathologist at the heart of cervical and ovarian cancer prevention.