bims-ovdlit 2024-05-19 papers

Issue of 2024–05–19
four papers selected by
Lara Paracchini, Humanitas Research

Gynecol Oncol. 2024 May 16. pii: S0090-8258(24)00222-1. [Epub ahead of print]187 113-119

Does serous tubal intraepithelial carcinoma (STIC) metastasize? The clonal relationship between STIC and subsequent high-grade serous carcinoma in BRCA1/2 mutation carriers several years after risk-reducing salpingo-oophorectomy.

C B van den Berg, S Dasgupta, P C Ewing-Graham, J Bart, J Bulten, K N Gaarenstroom, J A de Hullu, C H Mom, M J E Mourits, M P Steenbeek, R van Marion, H J van Beekhuizen.

OBJECTIVE: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood.
METHODS: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing.
RESULTS: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months).
CONCLUSION: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize.

Keywords: BRCA1/2; Clonality; High-grade serous carcinoma; Next-generation sequencing; Serous tubal intra-epithelial carcinoma; TP53

DOI: https://doi.org/10.1016/j.ygyno.2024.05.010

Int J Cancer. 2024 May 13.

High performance of the DNA methylation-based WID-qEC test for detecting uterine cancers independent of sampling modalities.

Ojone Illah, Malcolm Scott, Elisa Redl, James E Barrett, Lena Schreiberhuber, Chiara Herzog, Charlotte D Vavourakis, Allison Jones, Iona Evans, Dan Reisel, Dhivya Chandrasekaran, Kostas Doufekas, Radha Graham, Ioannis C Kotsopoulos, Nicola MacDonald, Rupali Arora, Adeola Olaitan, Adam Rosenthal, Martin Widschwendter.

Endometrial cancer (EC) is the most prevalent gynaecological cancer in high-income countries and its incidence is continuing to rise sharply. Simple and objective tools to reliably detect women with EC are urgently needed. We recently developed and validated the DNA methylation (DNAme)-based women's cancer risk identification-quantitative polymerase chain reaction test for endometrial cancer (WID-qEC) test that could address this need. Here, we demonstrate that the stability of the WID-qEC test remains consistent regardless of: (i) the cervicovaginal collection device and sample media used (Cervex brush and PreservCyt or FLOQSwab and eNAT), (ii) the collector of the specimen (gynaecologist- or patient-based), and (iii) the precise sampling site (cervical, cervicovaginal and vaginal). Furthermore, we demonstrate sample stability in eNAT medium for 7 days at room temperature, greatly facilitating the implementation of the test into diagnostic laboratory workflows. When applying FLOQSwabs (Copan) in combination with the eNAT (Copan) sample collection media, the sensitivity and specificity of the WID-qEC test to detect uterine (i.e., endometrial and cervical) cancers in gynaecologist-taken samples was 92.9% (95% confidence interval [CI] = 75.0%-98.8%) and 98.6% (95% CI = 91.7%-99.9%), respectively, whilst the sensitivity and specificity in patient collected self-samples was 75.0% (95% CI = 47.4%-91.7%) and 100.0% (95% CI = 93.9%-100.0%), respectively. Taken together these data confirm the robustness and clinical potential of the WID-qEC test.

Keywords: DNA methylation; collection modalities; early detection; endometrial cancer

DOI: https://doi.org/10.1002/ijc.35000

Nat Rev Clin Oncol. 2024 May 17.

Epidemiology of HPV-associated cancers past, present and future: towards prevention and elimination.

Talía Malagón, Eduardo L Franco, Romina Tejada, Salvatore Vaccarella.

Cervical cancer is the first cancer deemed amenable to elimination through prevention, and thus lessons from the epidemiology and prevention of this cancer type can provide information on strategies to manage other cancers. Infection with the human papillomavirus (HPV) causes virtually all cervical cancers, and an important proportion of oropharyngeal, anal and genital cancers. Whereas 20th century prevention efforts were dominated by cytology-based screening, the present and future of HPV-associated cancer prevention relies mostly on HPV vaccination and molecular screening tests. In this Review, we provide an overview of the epidemiology of HPV-associated cancers, their disease burden, how past and contemporary preventive interventions have shaped their incidence and mortality, and the potential for elimination. We particularly focus on the cofactors that could have the greatest effect on prevention efforts, such as parity and human immunodeficiency virus infection, as well as on social determinants of health. Given that the incidence of and mortality from HPV-associated cancers remain strongly associated with the socioeconomic status of individuals and the human development index of countries, elimination efforts are unlikely to succeed unless prevention efforts focus on health equity, with a commitment to both primary and secondary prevention.

DOI: https://doi.org/10.1038/s41571-024-00904-z