bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2024–09–29
eight papers selected by
Lara Paracchini, Humanitas Research
  1. Improving specificity for ovarian cancer screening using a novel extracellular vesicle-based blood test - Performance in a training and verification cohort.
  2. Efficacy of PARP inhibitors in advanced high-grade serous ovarian cancer according to BRCA domain mutations and mutation type.
  3. ESMO Congress 2024.
  4. Enhancing the Polygenic Score Catalog with tools for score calculation and ancestry normalization.
  5. Human Papillomavirus-Associated Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.
  6. Will methylation assays be part of a full molecular strategy to improve clinical management of cervical neoplasia?
  7. Pathology of the Salpinx: A Retrospective Literature Review.
  8. Real-world application of comprehensive genomic profiling for gynecological malignancies: a multicenter observational study.
  1. J Mol Diagn. 2024 Sep 24. pii: S1525-1578(24)00208-3. [Epub ahead of print]
    Improving specificity for ovarian cancer screening using a novel extracellular vesicle-based blood test - Performance in a training and verification cohort.
    Emily S Winn-Deen, Laura T Bortolin, Daniel Gusenleitner, Kelly M Biette, Karen Copeland, Aleksandra Gentry-Maharaj, Sophia Apostolidou, Anthony D Couvillon, Daniel P Salem, Sanchari Banerjee, Jonian Grosha, Ibukunoluwapo O Zabroski, Christopher R Sedlak, Delaney M Byrne, Bilal F Hamzeh, MacKenzie S King, Lauren T Cuoco, Peter A Duff, Brendan J Manning, Troy B Hawkins, Dawn Mattoon, Toumy Guettouche, Steven J Skates, Amy Jamieson, Jessica N McAlpine, David Huntsman, Usha Menon.
      The low incidence of ovarian cancer (OC) dictates that any screening strategy needs to be both highly sensitive and highly specific. This study explored the utility of detecting multiple colocalized proteins or glycosylation epitopes on single tumor-associated extracellular vesicles (EVs) from blood. The novel OC Test employs immunoaffinity capture of tumor-associated EVs followed by proximity-ligation qPCR to detect combinations of up to three biomarkers to maximize specificity and measures multiple combinations to maximize sensitivity. A high-grade serous carcinoma (HGSC) case-control training set of EDTA plasma samples from 397 women was used to lock down the test design, the data interpretation algorithm, and the cut-off between cancer and non-cancer. Performance was verified and compared to CA125 in an independent blinded case-control set of serum samples from 390 women (132 controls, 66 HGSC, 83 non-HGSC OC, 109 benign). In the verification study, the OC Test showed a specificity of 97.0% (128/132; 95% CI: 92.4%-99.6%), a HGSC sensitivity of 97.0% (64/66; 95% CI: 87.8%-99.2%), and an AUC of 0.97 (95% CI 0.93-0.99) and also detected 73.5% (61/83; 95% CI: 62.7%-82.6%) of the non-HGSC OC cases. This test exhibited fewer false positives in subjects with benign ovarian tumors, non-ovarian cancers, and inflammatory conditions when compared to CA125. The combined sensitivity and specificity of this new test suggests it may have potential in OC screening.
    DOI:  https://doi.org/10.1016/j.jmoldx.2024.09.001
  2. Front Oncol. 2024 ;14 1412807
    Efficacy of PARP inhibitors in advanced high-grade serous ovarian cancer according to BRCA domain mutations and mutation type.
    Roberto Buonaiuto, Giuseppe Neola, Aldo Caltavituro, Alessandra Longobardi, Federica Pia Mangiacotti, Amedeo Cefaliello, Maria Rosaria Lamia, Francesco Pepe, Jole Ventriglia, Umberto Malapelle, Giancarlo Troncone, Mario Giuliano, Grazia Arpino, Sandro Pignata, Carmine De Angelis.
       Objective: Preclinical studies have emphasized the potential connection between BRCA specific domains defects and the activity of Poly ADP-ribose polymerase inhibitors (PARPi). Nevertheless, real-world evidence regarding the impact of BRCA domain defects and mutations on PARPi efficacy are limited. The aim of his study was to evaluate the efficacy of PARPi in terms of progression free survival (PFS) according to BRCA domains defects and mutation types.
    Methods: A retrospective analysis was performed among 79 BRCA mutated patients, diagnosed with advanced High-grade serous ovarian carcinoma (HGSOC) who received first- and second-line platinum- based chemotherapy followed by PARPi maintenance treatment. PFS was evaluated according to BRCA1 [Really Interesting Gene (RING), DNA Binding (DBD), Serine Cluster (SCD), BRCA1 C-terminal (BRCT)] and BRCA2 [RAD-51 Domain (RAD-51 BD), DBD] specific domain defects and mutation types [missense (MS), nonsense (NS), frameshift (FS), splicing (S), or large rearrangements (LR)].
    Results: After a median follow-up of 51 months, no significant difference in PFS was observed between the BRCA functional domains or mutation types in the BRCA1 and BRCA2 subgroups. Patients with BRCA2 DBD and RAD51-BD defects had the longest (39.8 months) and shortest (24.1 months) median PFS, respectively (p = 0.11). Additionally, patients with BRCA1 DBD defects had the greatest benefit (median PFS = 33.8 months) while those with BRCA1 RING domain mutations experienced the worst outcome (median PFS = 30.9 months (p = 0.43).
    Conclusion: The efficacy of maintenance treatment with PARPi is independent by BRCA domain defects or mutation types. Patients DBD domain defects experienced numerically longer median PFS compared to those with other BRCA1/2 alterations.
    Keywords:  BRCA mutation domain; HGSOC; PARP inhibitors; ovarian cancer; resistance
    DOI:  https://doi.org/10.3389/fonc.2024.1412807
  3. Lancet Oncol. 2024 Sep 19. pii: S1470-2045(24)00527-8. [Epub ahead of print]
    ESMO Congress 2024.
    Cheryl Lai.
      
    DOI:  https://doi.org/10.1016/S1470-2045(24)00527-8
  4. Nat Genet. 2024 Sep 26.
    Enhancing the Polygenic Score Catalog with tools for score calculation and ancestry normalization.
    Samuel A Lambert, Benjamin Wingfield, Joel T Gibson, Laurent Gil, Santhi Ramachandran, Florent Yvon, Shirin Saverimuttu, Emily Tinsley, Elizabeth Lewis, Scott C Ritchie, Jingqin Wu, Rodrigo Cánovas, Aoife McMahon, Laura W Harris, Helen Parkinson, Michael Inouye.
      
    DOI:  https://doi.org/10.1038/s41588-024-01937-x
  5. medRxiv. 2024 Sep 10. pii: 2024.09.10.24313140. [Epub ahead of print]
    Human Papillomavirus-Associated Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.
    Brian Y Zhao, Shun Hirayama, Deborah Goss, Yan Zhao, Daniel L Faden.
       Objective: Human papillomavirus (HPV) is known to affect head and neck sites beyond the oropharynx, including the nasopharynx. Unlike HPV-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC), HPV-associated nasopharyngeal carcinoma (HPV+NPC) is not well characterized and the true prevalence in non-endemic regions is poorly described. Here, we sought to obtain a global point prevalence of HPV in NPC, stratified by geographic region.
    Data Sources: EMBASE, OVID Medline, and Web of Science were systematically searched for available evidence on September 21, 2022 for articles published between January 1, 1990 and September 21, 2022.
    Review Methods: We reviewed the literature for all studies examining NPC and HPV status in adult patients that provided a quantitative HPV prevalence. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Main outcome and measures included HPV+NPC prevalence estimates stratified by geographic region, along with other clinical and demographic features.
    Results: Of the 1567 citations retrieved, 46 studies encompassing 6314 NPC patients were eligible for statistical analysis. The global prevalence of HPV+NPC was 0.18 (95% CI 0.14-0.23). When stratified by geographic region, prevalence was highest in North America (0.25, 95% CI 0.17-0.36), which is a non-endemic region for NPC and also has highest prevalence for HPV+OPSCC. Asia, an endemic area, had the lowest HPV prevalence estimate (0.13, 95% CI 0.08-0.22). HPV 16 (44%) and 18 (33%) were the predominant genotypes in HPV+NPC, dissimilar to HPV+OPSCC.
    Conclusion: This systematic review and meta-analysis provides a global point prevalence of HPV+NPC stratified by geographic region and suggests that HPV is a significant etiological factor of NPC in North America.
    DOI:  https://doi.org/10.1101/2024.09.10.24313140
  6. Epigenomics. 2024 Sep 25. 1-5
    Will methylation assays be part of a full molecular strategy to improve clinical management of cervical neoplasia?
    Mariam El-Zein, Eduardo L Franco.
      
    Keywords:  DNA methylation; cervical cancer management; cervical cancer screening; cervical intraepithelial neoplasia; human papillomavirus
    DOI:  https://doi.org/10.1080/17501911.2024.2402684
  7. Cureus. 2024 Aug;16(8): e67624
    Pathology of the Salpinx: A Retrospective Literature Review.
    Itunujesu J Olonade, Adeola Adegunle, Suma Maj Kaza.
      The fallopian tube is a common surgical specimen, yet there is limited research on the histomorphologic findings. This study seeks to review the various abnormalities found in the fallopian tube and establish the primary disease processes linked to it. These findings can provide valuable insights for future preventive healthcare measures. Utilizing PubMed, a search was conducted for articles published between 2009 and 2024 to investigate fallopian tube pathologies using case reports. The inclusion criteria focused on patients older than 18 years with confirmed or incidental fallopian tube pathology diagnoses. The study considered both common and uncommon presentations of fallopian tube pathologies, with a primary focus on identifying the presenting symptoms related to these conditions, such as primary infertility, severe abdominal pain, tachycardia, hypotension, and breathlessness (the last three could indicate a surgical emergency with ruptured ectopic pregnancy and subsequent hemoperitoneum). Fifteen studies were included in this review. The findings revealed three cases of genital tuberculosis, two cases of endometriosis, two cases of fallopian tube prolapse, three cases of ovarian cancer, and four cases of ectopic pregnancy. To confirm the presence of these conditions, histopathological examination was performed using specimens obtained through salpingectomy/salpingostomy. This study effectively highlighted the occurrence of rare presentations associated with common fallopian tube pathologies. By identifying different pathologies present in the fallopian tube, healthcare professionals can expand the range of existing pathologies that may be considered as potential differential diagnoses. This knowledge is essential in directing patient care and has the potential to improve patient outcomes significantly.
    Keywords:  ectopic pregnancy; fallopian tube endometriosis; fallopian tube prolapse; fallopian tubes; female genital tuberculosis; ovarian cancer
    DOI:  https://doi.org/10.7759/cureus.67624
  8. Int J Clin Oncol. 2024 Sep 25.
    Real-world application of comprehensive genomic profiling for gynecological malignancies: a multicenter observational study.
    Mayu Fukuda, Koji Yamanoi, Nobutaka Hayashi, Yasushi Kotani, Kazuki Yamano, Hisanori Matsumoto, Takahito Ashihara, Kaoru Abiko, Yukio Yamanishi, Yoko Iemura, Mana Taki, Ryusuke Murakami, Akihito Horie, Ken Yamaguchi, Junzo Hamanishi, Masaki Mandai.
       BACKGROUND: The actual status of comprehensive genomic profiling (CGP) applications in Japan has not been clarified. We conducted a multicenter study to investigate the real-world application of CGP in gynecological malignancies.
    METHODS: Nine designated cancer hospitals participated in this study. Patients who underwent CGP in 2020-2021 were assigned to the CGP group (n = 134). For the population that would have been eligible for CGP, patients who received initial treatment in 2015-2016 and were either alive with disease or died of disease at 5 years follow up were included in the control group (n = 316). We compared clinicopathological characteristics including tumor type (cervix, corpus, ovary, and others including sarcoma) and age. We also investigated the context of CGP-recommended treatment.
    RESULTS: The CGP group had significantly fewer cervical cases and more others cases (cervix/corpus/ovary/others: CGP, 22/44/56/12; control, 89/79/142/6; p = 0.0003). The CGP group was significantly younger than the control group (median: CGP, 54.0; control, 65.0; p < 0.0001). Subgroup analyses revealed that patients with cervical and ovarian cancers were significantly younger in the CGP group. Among the CGP group, 17 patients (12.7%) received CGP-recommended treatments, 15 of which were not covered by public insurance. The survival time after CGP in 17 patients was longer than in the other 117 cases (median 21 vs. 11 months).
    CONCLUSION: There was significant selection bias in tumor type and age for the application of CGP for gynecological malignancies in clinical practice in Japan. While CGP often recommended drugs not covered by public insurance, prognosis can be improved by use of CGP.
    Keywords:  Age; Comprehensive genomic profiling; Gynecological malignancies; Selection bias; Tumor type
    DOI:  https://doi.org/10.1007/s10147-024-02628-7
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