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Cancer and Immunology

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Cancer and Immunology

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Patient Care

Abstract

Background: Ovarian cancer (OC) remains the gynecologic cancer with the highest mortality due to late-stage diagnosis, lack of effective screening tools, and nonspecific symptoms. This literature review evaluates the use of Pap smears and cervicovaginal fluids for early OC detection. This review explores their potential for detecting OC-specific biomarkers, mutations, proteomics, and methylation patterns from Pap smears and cervicovaginal fluids to investigate their effectiveness and utility as screening and diagnostic tools for OC.

Methods: A systematic PubMed search was conducted using keywords related to ovarian cancer diagnosis, Pap smears, early detection, cervical swabs, mutations, and methylation. Eligibility criteria focused on English clinical trials, systematic reviews, and both quantitative and qualitative data from 2013-2024. From 47 identified articles, relevant studies were selected based on titles, abstracts, and full-text reviews. Articles were sub-categorized within diagnostic techniques to include methylation, proteomics, gene mutations, and case study. Key findings on the feasibility and accuracy of OC detection using Pap smears and cervicovaginal samples were summarized for data extraction.

Results: 1. DNA Methylation: Hypermethylation of POU4F3 and MAGI2 demonstrated 61% sensitivity for OC detection, with POU4F3 showing 69% specificity and MAGI2 62% specificity. Methylation of AMPD3, AOX1, NRN1, and TBX15 exhibited high accuracy for OC detection. An OC-risk score of AMPD3, NRN1, and TBX15 achieved 81% sensitivity, 84% specificity. A logistic regression model using methylation data with these markers showed 81.0% sensitivity and 84.2% specificity for OC detection. Pap smears detected OC with 50% sensitivity compared to plasma samples.

2. DNA Mutations: TP53 mutations were found in 37.5% of Pap tests from women with high-grade serous carcinoma (HGSC). TP53 mutations were detected in 6 of 8 diagnostic samples and in one sample collected 20 months before diagnosis. OC tumors showed hotspot mutations in 16 of 17 cases, with 50% of Pap smears matching these mutations. PapGene identified TP53, CSMD3, and FAT3 mutations in 41% of OC cases via Pap smears.

3. Proteomics: An 11-protein panel from cervicovaginal fluids differentiated OC cases from controls with a sensitivity of 0.97 and specificity of 0.67, with MUCIN-16 and WFDC2 detected in 16% and 64% of ovarian cancer samples, respectively. A panel of five peptides demonstrated significant ability to distinguish between OC and benign pelvic masses, achieving an AUC of 0.86.

4. Case Study: A woman with a recent diagnosis of triple-negative invasive ductal breast carcinoma underwent a routine Pap smear that identified malignant cells not originating from the breast or cervix. This led to the detection of early-stage HGSOC, a rare early detection of ovarian cancer with no other abnormal findings present.

Conclusions: Pap smears and cervicovaginal samples for OC screening shows promise as a noninvasive, cost-effective method for early detection. Initial studies highlight promising results concerning methylation patterns and gene mutations related to OC. Further research is needed to enhance test specificity and sensitivity and include larger sample sizes. Further, this method may not detect all OC subtypes. With more research, this approach could significantly improve early detection, screening practices, and ultimately, patient survival rates.

Presentation Type

Poster

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Oncology Commons

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Utilization of Pap Smears and Cervicovaginal Fluid for Early Ovarian Cancer Screening & Detection

Background: Ovarian cancer (OC) remains the gynecologic cancer with the highest mortality due to late-stage diagnosis, lack of effective screening tools, and nonspecific symptoms. This literature review evaluates the use of Pap smears and cervicovaginal fluids for early OC detection. This review explores their potential for detecting OC-specific biomarkers, mutations, proteomics, and methylation patterns from Pap smears and cervicovaginal fluids to investigate their effectiveness and utility as screening and diagnostic tools for OC.

Methods: A systematic PubMed search was conducted using keywords related to ovarian cancer diagnosis, Pap smears, early detection, cervical swabs, mutations, and methylation. Eligibility criteria focused on English clinical trials, systematic reviews, and both quantitative and qualitative data from 2013-2024. From 47 identified articles, relevant studies were selected based on titles, abstracts, and full-text reviews. Articles were sub-categorized within diagnostic techniques to include methylation, proteomics, gene mutations, and case study. Key findings on the feasibility and accuracy of OC detection using Pap smears and cervicovaginal samples were summarized for data extraction.

Results: 1. DNA Methylation: Hypermethylation of POU4F3 and MAGI2 demonstrated 61% sensitivity for OC detection, with POU4F3 showing 69% specificity and MAGI2 62% specificity. Methylation of AMPD3, AOX1, NRN1, and TBX15 exhibited high accuracy for OC detection. An OC-risk score of AMPD3, NRN1, and TBX15 achieved 81% sensitivity, 84% specificity. A logistic regression model using methylation data with these markers showed 81.0% sensitivity and 84.2% specificity for OC detection. Pap smears detected OC with 50% sensitivity compared to plasma samples.

2. DNA Mutations: TP53 mutations were found in 37.5% of Pap tests from women with high-grade serous carcinoma (HGSC). TP53 mutations were detected in 6 of 8 diagnostic samples and in one sample collected 20 months before diagnosis. OC tumors showed hotspot mutations in 16 of 17 cases, with 50% of Pap smears matching these mutations. PapGene identified TP53, CSMD3, and FAT3 mutations in 41% of OC cases via Pap smears.

3. Proteomics: An 11-protein panel from cervicovaginal fluids differentiated OC cases from controls with a sensitivity of 0.97 and specificity of 0.67, with MUCIN-16 and WFDC2 detected in 16% and 64% of ovarian cancer samples, respectively. A panel of five peptides demonstrated significant ability to distinguish between OC and benign pelvic masses, achieving an AUC of 0.86.

4. Case Study: A woman with a recent diagnosis of triple-negative invasive ductal breast carcinoma underwent a routine Pap smear that identified malignant cells not originating from the breast or cervix. This led to the detection of early-stage HGSOC, a rare early detection of ovarian cancer with no other abnormal findings present.

Conclusions: Pap smears and cervicovaginal samples for OC screening shows promise as a noninvasive, cost-effective method for early detection. Initial studies highlight promising results concerning methylation patterns and gene mutations related to OC. Further research is needed to enhance test specificity and sensitivity and include larger sample sizes. Further, this method may not detect all OC subtypes. With more research, this approach could significantly improve early detection, screening practices, and ultimately, patient survival rates.

 

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