bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2024‒10‒13
ten papers selected by
Lara Paracchini, Humanitas Research



  1. Oral Oncol. 2024 Oct 08. pii: S1368-8375(24)00375-0. [Epub ahead of print]159 107057
      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.
    Keywords:  Human papillomavirus; Nasopharyngeal carcinoma
    DOI:  https://doi.org/10.1016/j.oraloncology.2024.107057
  2. Mod Pathol. 2024 Oct 08. pii: S0893-3952(24)00209-6. [Epub ahead of print] 100629
      The current paradigm implicates a fallopian tube precursor as the origin of most ovarian high-grade serous carcinomas (HGSC). However, a rare subset of HGSCs develop via a distinct pathway from low-grade serous ovarian neoplasms (namely, serous borderline tumor and low-grade serous carcinoma). This alternate pathway for the development of HGSC and other poorly differentiated carcinomas of the ovary is not well understood. To elucidate the molecular pathogenesis and evolutionary trajectory of histologic transformation of low-grade serous neoplasms, we performed whole exome sequencing on microdissected low-grade and higher-grade components from 7 cases of serous borderline tumor or low-grade serous carcinoma associated with a synchronous or metachronous indeterminate/high-grade carcinoma. In most cases, there were relatively few somatic mutations shared between matched low-grade and higher-grade tumors compared to private mutations specific to each component (i.e., phylogenetic trees with short trunks and long branches). Truncal mutations, present across all tumor samples from a given patient, included known drivers of low-grade serous neoplasms: KRAS (G12D, n=4), BRAF (G469A, n=1), NF2 (n=1), and USP9X (n=1). Transformation to HGSC was associated with a TP53 mutation with bi-allelic inactivation in 3 cases, all with severe nuclear atypia, and associated with genome-wide copy number alterations and allelic imbalances. TP53-wildtype tumors comprised a morphologic spectrum, which included indeterminate-grade serous carcinomas with moderate nuclear atypia and high mitotic activity, while lacking extensive chromosomal instability (n=2), and poorly-differentiated carcinomas (n=2, including a high-grade Mullerian carcinoma and an undifferentiated carcinoma with sarcomatoid features). In summary, synchronous and metachronous low-grade serous neoplasms and higher-grade carcinomas are clonally related. Early genetic divergence, most evident in cases with TP53 mutations, suggests that high-grade transformation may be a relatively early molecular event.
    DOI:  https://doi.org/10.1016/j.modpat.2024.100629
  3. Ann Oncol. 2024 Sep 14. pii: S0923-7534(24)03929-2. [Epub ahead of print]
      BACKGROUND: Outcomes for patients with locally advanced head and neck cancer (HNC) treated with curative intent remain disappointing, with 5-year survival rates at 50%. Most recurrences occur within the first 2 years after treatment, providing a window of opportunity to identify patients with molecular residual disease (MRD). A tissue-agnostic test for MRD detection in patients with human papillomavirus (HPV) positive and negative HNC, where tissue is often scarce, is needed.PATIENTS AND METHODS: Patients with stage I-IVB HNC, including patients positive and negative for HPV, were enrolled and peripheral blood plasma was collected longitudinally at diagnosis and ∼3, 12, and 24 months after curative intent treatment. The full cohort includes 325 patients with 1155 samples. Samples were split into distinct sets to train and validate a classifier capable of identifying MRD using a tissue-agnostic genome-wide methylome enrichment platform. The primary endpoint was recurrence-free survival (RFS).
    RESULTS: With a median follow-up of 60 months, patients in the blinded validation set with MRD positivity experienced significantly worse RFS with a hazard ratio (HR) of 35.7 [95% confidence interval (CI) 10.8-117.8; P < 0.0001]. For patients with HPV negativity, HR was 42.3 (95% CI 9.8-182.3; P < 0.0001); for patients with HPV-positive oropharyngeal cancer, HR was 24.1 (95% CI 3.0-196.8; P < 0.0001). Moreover, the lead time between MRD positivity and clinical recurrence was up to 14.9 months, with a mean lead time of 4.1 months. Surveillance sensitivity was 91% (95% CI 77% to 97%) and specificity was 88% (95% CI 80% to 93%).
    CONCLUSIONS: Here we validate the clinical performance characteristics of a tissue-agnostic genome-wide methylome enrichment assay for MRD detection in patients with HNC. The MRD detection test showed high sensitivity for identifying recurrence at high specificity across different anatomical sites, HPV status, and treatment regimens, highlighting the broad applicability for MRD detection in patients with HNC.
    Keywords:  cfDNA; cfMeDIP-seq; head and neck cancer; liquid biopsy; molecular residual disease; precision medicine
    DOI:  https://doi.org/10.1016/j.annonc.2024.08.2348
  4. STAR Protoc. 2024 Oct 03. pii: S2666-1667(24)00522-7. [Epub ahead of print]5(4): 103357
      Circulating cell-free DNA (cfDNA) fragment end motif profiles are a promising biomarker in precision oncology. Here, we present a protocol for analyzing plasma cfDNA fragment end motifs from ultra-low-pass whole-genome sequencing (WGS) data. We detail a pipeline composed of sequential bash scripts for processing post-alignment BAM files. Subsequently, we outline the procedure for downstream analysis and visualization of 4-mer as well as other n-mer cfDNA end motifs in R. For complete details on the use and execution of this protocol, please refer to Liu et al.1.
    Keywords:  Cancer; Genomics; Sequence analysis; Sequencing
    DOI:  https://doi.org/10.1016/j.xpro.2024.103357
  5. Biomed Phys Eng Express. 2024 Sep 30. 10(6):
      Cervical cancer remains a major global health challenge, accounting for significant morbidity and mortality among women. Early detection through screening, such as Pap smear tests, is crucial for effective treatment and improved patient outcomes. However, traditional manual analysis of Pap smear images is labor-intensive, subject to human error, and requires extensive expertise. To address these challenges, automated approaches using deep learning techniques have been increasingly explored, offering the potential for enhanced diagnostic accuracy and efficiency. This research focuses on improving cervical cancer detection from Pap smear images using advanced deep-learning techniques. Specifically, we aim to enhance classification performance by leveraging Transfer Learning (TL) combined with an attention mechanism, supplemented by effective preprocessing techniques. Our preprocessing pipeline includes image normalization, resizing, and the application of Histogram of Oriented Gradients (HOG), all of which contribute to better feature extraction and improved model performance. The dataset used in this study is the Mendeley Liquid-Based Cytology (LBC) dataset, which provides a comprehensive collection of cervical cytology images annotated by expert cytopathologists. Initial experiments with the ResNet model on raw data yielded an accuracy of 63.95%. However, by applying our preprocessing techniques and integrating an attention mechanism, the accuracy of the ResNet model increased dramatically to 96.74%. Further, the Xception model, known for its superior feature extraction capabilities, achieved the best performance with an accuracy of 98.95%, along with high precision (0.97), recall (0.99), and F1-Score (0.98) on preprocessed data with an attention mechanism. These results underscore the effectiveness of combining preprocessing techniques, TL, and attention mechanisms to significantly enhance the performance of automated cervical cancer detection systems. Our findings demonstrate the potential of these advanced techniques to provide reliable, accurate, and efficient diagnostic tools, which could greatly benefit clinical practice and improve patient outcomes in cervical cancer screening.
    Keywords:  cervical cancer; histogram of oriented gradients; self-attention; transfer learning
    DOI:  https://doi.org/10.1088/2057-1976/ad7bc0
  6. J Med Genet. 2024 Oct 11. pii: jmg-2024-110385. [Epub ahead of print]
      
    Keywords:  DNA Repair; Early Diagnosis; Gastroenterology; Genetic Predisposition to Disease; Genomic Instability
    DOI:  https://doi.org/10.1136/jmg-2024-110385
  7. Nat Rev Genet. 2024 Oct 07.
      Decades of genetic association testing in human cohorts have provided important insights into the genetic architecture and biological underpinnings of complex traits and diseases. However, for certain traits, genome-wide association studies (GWAS) for common SNPs are approaching signal saturation, which underscores the need to explore other types of genetic variation to understand the genetic basis of traits and diseases. Copy number variation (CNV) is an important source of heritability that is well known to functionally affect human traits. Recent technological and computational advances enable the large-scale, genome-wide evaluation of CNVs, with implications for downstream applications such as polygenic risk scoring and drug target identification. Here, we review the current state of CNV-GWAS, discuss current limitations in resource infrastructure that need to be overcome to enable the wider uptake of CNV-GWAS results, highlight emerging opportunities and suggest guidelines and standards for future GWAS for genetic variation beyond SNPs at scale.
    DOI:  https://doi.org/10.1038/s41576-024-00778-y
  8. Nature. 2024 Oct;634(8033): 298
      
    Keywords:  Cancer; Genomics; Policy; Public health
    DOI:  https://doi.org/10.1038/d41586-024-03268-7
  9. Clin Obstet Gynecol. 2024 Oct 07.
      Hereditary cancer syndromes (HCS) are responsible for up to 10% of all cancers. At present, the majority of cancer susceptibility testing is initiated after a cancer diagnosis. There exists a significant opportunity for primary care providers including general obstetrician-gynecologists to engage in hereditary cancer risk assessment through adequate family history evaluation, initiation of genetic testing, and following the recommendations of national organizations. Identifying hereditary cancer genes may prompt primary prevention efforts such as enhanced screening, prevention, or personalized care strategies. We will review the literature regarding the approach and assessment of the most common gynecologic HCS.
    DOI:  https://doi.org/10.1097/GRF.0000000000000894
  10. Nature. 2024 Oct 07.
      
    Keywords:  Funding; Peer review; Publishing; Research management
    DOI:  https://doi.org/10.1038/d41586-024-03106-w