Jeffrey K Mito

Genomic catastrophe, the peritoneal cavity and ovarian cancer prevention

AbstractThe current theory of carcinogenesis for the deadliest of ‘ovarian’ cancers—high‐grade serous carcinoma (HGSC)—holds that the malignancy develops first in the fallopian tube and spreads to the ovaries, peritoneum, and/or regional lymph nodes. This is based primarily on the observation of early forms of serous neoplasia (serous tubal intraepithelial lesions [STILs], and serous tubal intraepithelial carcinomas [STICS]) in the fimbria of women undergoing risk reduction surgery. However, these lesions are uncommon in the general population, confer a low risk (5%) of HGSC following their removal in at‐risk women with germ‐line BRCA1/2 mutations, and require 4 or more years to recur as intraperitoneal HGSC. These features suggest that isolated STILs and STICs behave as precursors, with uncertain cancer risk rather than carcinomas. Their evolution to HGSC within, or after, escape from the tube could proceed stepwise with multiple biologic events; however, it is unclear whether tubal or ovarian HGSCs encountered in the setting of advanced disease evolved in the same fashion. The latter scenario could also be explained by a ‘catastrophic’ model in which STICs suddenly develop with invasive and metastatic potential, overwhelming or obscuring the site of origin. Moreover, a similar model might explain the sudden emergence of HGSC in the peritoneal cavity following escape of precursor cells years before. Long‐term follow‐up data from opportunistic or prophylactic salpingectomy should shed light on where malignant transformation occurs, as well as the timeline from precursor to metastatic HGSC. © 2022 The Pathological Society of Great Britain and Ireland.

Triage options for positive high-risk HPV results from HPV-based cervical cancer screening: a review of the potential alternatives to Papanicolaou test cytology

The American Cancer Society has recommended high-risk human papillomavirus (HPV) testing as the primary screening method for cervical cancer since 2020. Up to this point, the transition from Pap test cytology-based screening or co-testing with cytology and HPV testing has been slow and limited. However, more health systems in the United States are in the process of implementing this change. The transition to HPV-based screening requires a triage strategy for positive results. Genotyping to specifically detect HPV types 16 and 18 in conjunction with reflex cytology for the remaining high-risk HPV genotypes has been the recommended method. Testing options including Dual Stain for p16/Ki-67 and extended HPV genotyping are currently being incorporated into treatment algorithms as alternatives. Methylation testing is another promising method extensively investigated around the world. This review, performed by members of the Clinical Practice Committee of the American Society of Cytopathology, examines the rationale behind the switch away from reliance on Pap test cytology in the cervical cancer screening algorithm and the opportunities and problems associated with the most promising alternative approaches. Published studies that give insight into the performance characteristics of these newer tests are reviewed. At the present time, Pap test cytology remains a viable triage option for positive HPV screening results, but alternative tests have significant appeal and should be considered in tandem with the decision to offer primary HPV screening.