Positive DNA Test Research Articles

Hepatitis Delta Coinfection Rates and All-Cause Mortality Among Hepatitis B-Infected Veterans in the USA.

Screening for hepatitis D virus (HDV) is recommended for all individuals with hepatitis B virus (HBV) infection. Coinfected individuals experience more severe liver-related outcomes. We determined the HDV testing and coinfection rates and all-cause mortality among those infected with HBV. We used the US Department of Veterans Affairs (VA) healthcare system's national databases to identify individuals with HBV infection. We determined the proportion of individuals referred to gastroenterologists/hepatologists, or infectious diseases providers, and the proportion screened and tested positive for HDV. We calculated the HBV treatment rates, defined as ≥ 3 months of continuous prescription with an approved drug. Finally, we calculated all-cause mortality stratified by HDV coinfection and HBV treatment status. Among 44,951 individuals with at least one positive HBsAg, HBeAg or HBV DNA test, 5964 (13.3%) were screened for HDV (180 [3.0%] tested positive), and 28,291 (62.9%) were referred to gastroenterology/hepatology or infectious diseases. Treatment for HBV was prescribed for 73 (40.5%) of HDV-coinfected and 2425 (41.9%) HDV-uninfected individuals. All-cause mortality rate per 100 person-years was lower among those without HDV coinfection (2.98 for untreated HBV, 2.53 for treated HBV; p < 0.001) compared with those with HDV coinfection (5.14 for untreated HBV, 3.0 for treated HBV; p = 0.02). Kaplan-Meier curves demonstrated a significantly higher mortality among HDV-coinfected individuals who were not treated for HBV (log-rank p < 0.0001). Screening rates for HDV among HBV-infected individuals are suboptimal. While HDV coinfection is associated with higher all-cause mortality, HBV treatment may confer a survival benefit.

Multisite Evaluation and Validation of Optical Genome Mapping for Prenatal Genetic Testing

Prenatal diagnostic testing of amniotic fluid, chorionic villi, or more rarely, fetal cord blood is recommended following a positive or unreportable noninvasive cell-free fetal DNA test, abnormal maternal biochemical serum screen, abnormal ultrasound, or increased genetic risk for a cytogenomic abnormality based on family history. Although chromosomal microarray is recommended as the first-tier prenatal diagnostic test, in practice, multiple assays are often assessed in concert to achieve a final diagnostic result. The use of multiple methodologies is costly, time consuming, and labor intensive. Optical genome mapping (OGM) is an emerging technique with application for prenatal diagnosis because of its ability to detect and resolve, in a single assay, all classes of pathogenic cytogenomic aberrations. In an effort to characterize the potential of OGM as a novel alternative to traditional standard of care (SOC) testing of prenatal samples, OGM was performed on a total of 200 samples representing 123 unique cases, which were previously tested with SOC methods (92/123=74.7% cases tested with at least two SOCs). OGM demonstrated an overall accuracy of 99.6% when compared with SOC methods, a positive predictive value of 100%, and 100% reproducibility between sites, operators, and instruments. The standardized workflow, cost-effectiveness, and high-resolution cytogenomic analysis demonstrate the potential of OGM to serve as a first-tier test for prenatal diagnosis.

Improving Barriers to Timely Colonoscopies: A New Approach to Overcoming Gaps in Medical Care.

This study investigates delays in transitioning from positive noninvasive multitarget stool DNA test results to scheduled diagnostic colonoscopies and identifies strategies aimed at improving patient care. A retrospective review revealed a 53% reduction in the average time from positive multitarget stool DNA test results to ordering colonoscopies postintervention. The findings demonstrate the significance of implementing a new communication system to expedite transitions in health care processes, showcasing its potential to significantly improve efficiency in patient care and health care provider workflows across various clinical testing scenarios. The findings emphasize the transformative impact of this communication system, shedding light on its ability to streamline processes and enhance patient care and staff experience.

Cervical Cancer Treatment Update: A Society of Gynecologic Oncology Clinical Practice Statement

ABSTRACT Despite increased screening and human papillomavirus (HPV) vaccination in high-income countries, cervical cancer represents the fourth most diagnosed cancer in women worldwide and the second highest cause of cancer mortality among women in low- and middle-income countries. This clinical practice statement describes therapies for cervical cancer by treatment setting, as well as quality of life, financial toxicity, and disparities associated with the disease. Persistent HPV infection, particularly types 16 and 18, are the main factor in the development of cervical cancer. High-risk HPV variants integrate HPV DNA into the host genome to upregulate two viral oncoproteins, E6 and E7, which in turn inhibit the tumor suppressor proteins p53 and Rb. Certain driver mutations including PIK3CA, KRAS, and EGFR are frequently seen in cervical cancer, however further research is needed to identify an actionable biomarker based on targetable oncogenic alterations. Locally advanced cervical cancer is defined as clinically visible tumor exceeding 4 cm or invading beyond the cervix, extending to the pelvic sidewalls, vagina, bladder, rectum, or involving pelvic and/or paraaortic lymph nodes. Standard treatment for locally advanced cervical cancer is external beam radiation therapy and concurrent weekly cisplatin. Standard treatment for advanced, recurrent, or metastatic cervical cancer is cisplatin, paclitaxel, and bevacizumab (possibly adding pembrolizumab). Several studies have shown that checkpoint inhibitors, when combined or sequenced with chemoradiation, may provide survival benefit in both locally advanced and recurrent/metastatic cervical cancer. Given these findings, immunotherapy should be incorporated in treatment of advanced or recurrent disease. Negative effects on quality of life (QOL) in patients with cervical cancer often begin in people who receive negative Papanicolaou test results or positive HPV DNA tests. Negative body image, self-esteem, and relationships with partners contribute to an overall decrease in QoL. Surgical, radiation-induced, and chemotherapy-induced treatment effects further impact survivors’ physical health, body-image, and sexual function. Economic burdens of cancer diagnosis and treatment may disproportionally affect cervical cancer patients due to the intensity of curative treatment, decreases in QoL and functional status, and unique population including younger patients, those with poor access to health care at baseline, and those who identify as racial or ethnic minorities.

The Role of β1 Integrin/CD29 as a Potential Prognostic Factor for the Risk of Progression to Cervical Carcinoma in HPV-Associated Lesions.

Background and Objectives: Available evidence reports the overexpression of β1 integrin in dysplastic rather than normal cervical tissue. We aimed to evaluate the involvement of β1 (CD29) integrin in the progressive pathogenesis of cervical intraepithelial neoplasia (CIN). Materials and Methods: From January 2019 to December 2021, we prospectively enrolled women undergoing a colposcopy with a cervical biopsy for abnormal cervical cytology and/or undefined cytology with a positive HPV DNA test and women with relapsing cervical inflammatory disorders. Based on the histopathological results, women were divided into four groups: group A (CIN1), group B (CIN2), group C (CIN3), and group D (no CIN diagnosis) as a control group. Subsequently, cytofluorimetry and immunohistochemical analysis (based on the identified positive cell ratios as follows: ≤10%, negative; 10-25%, 1+ (weak); 25-50%, 2+ (medium); ≥50%, and 3+ (high)) for β1 integrin were carried out. Results: In total, 154 women were included. The average fluorescence intensity in the four groups was 2.35 ± 1.37, 2.73 ± 1.56, 3.09 ± 1.56, and 2.13 ± 1.25 UA from groups A to D, respectively; this figure was significantly different for CIN3 (group C) women relative to the other groups (p = 0.0132). Higher β1 integrin/CD29 concentrations in the CIN groups with HR-HPV 16 and 18 were also detected (p = 0.0292, 0.0367, and 0.0357 respectively for CIN3, CIN2, and CIN1). Immunohistochemistry analysis showed higher results for the CIN3 group compared to controls and all the other groups (p < 0.001). Conclusions: β1/CD29 integrin expression increased with CIN grade, and it was significantly higher in CIN3 lesions. This could be used as a promising screening tool to identify women prone to developing high-grade cervical lesions. However, additional evidence is needed to strengthen these findings.

Prevalence of Hepatitis B Virus Markers among the Women with Breast Cancer.

Breast cancer represents a formidable peril to the female populace on a worldwide level. The association between breast cancer and various factors, including viral infections, has been extensively investigated. Recently, the link between HBV infection and breast cancer patients has garnered attention. The present research aims to assess the prevalence of HBV markers among women diagnosed with breast cancer in Ahvaz city, Iran. Serum specimens were procured from 90 patients who had been clinically diagnosed with breast cancer. The age of the patients ranged from 29 to 80 years, with a mean age of 49.42±10.7. Histological examination of biopsy specimens revealed that 75 (83.33%) were ductal, 11 (8.88%) lobular, 2 (2.22%) mucinous, 1 (1.11%) medullary, and 1 (1.11%) was metastatic. The serum samples were subjected to initial HBsAg and anti-HBc testing via ELISA. Samples that tested seropositive (HBsAg + anti-HBc) were subsequently analyzed for the S region of HBV through nested PCR and DNA sequencing. Finally, a phylogenetic tree was constructed for positive HBV DNA tests. Among the 5/90 (5.55%) cancer patients, it was found that 3 (3.33%) cases of ductal carcinoma and one (1.11%) lobular carcinoma displayed positivity for HBV markers (HBsAg, anti-HBc, HBV PCR). Notably, one (1.11%) patient with ductal carcinoma solely demonstrated anti-HBc positivity. The phylogenetic tree analysis of the S region revealed that all HBV strains identified were categorized as genotype D. The statistical analysis did not reveal any significant findings (p= 0.315) in the distribution of cancer types across different age groups. Among patients diagnosed with breast cancer, a notable prevalence of 5.5% was observed in HBV markers. The dominant HBV genotype among breast cancer patients was identified as genotype D.

Screening Practices and Risk Factors for Co-Infection with Latent Tuberculosis and Hepatitis B Virus in an Integrated Healthcare System — California, 2008-2019

BackgroundHepatitis B virus (HBV) and latent tuberculosis infection are associated with a significant global burden, but both are underdiagnosed and undertreated. We described the screening patterns and risk factors for co-infection with latent tuberculosis and HBV within a large healthcare system. MethodsUsing data from Kaiser Permanente Southern California during 2008-2019, we described HBV infections, defined as a positive HBV surface antigen, e-antigen, or DNA test, and latent tuberculosis, defined as a positive Mantoux tuberculin skin test or interferon-gamma release assay test. We estimated adjusted odds ratios (aOR) for co-infection among screened adults with either infection. ResultsAmong 1997 HBV patients screened for latent tuberculosis, 23.1% were co-infected, and among 35,820 patients with latent tuberculosis screened for HBV, 1.3% were co-infected. Among HBV patients, co-infection risk was highest among Asians compared with White race/ethnicity (29.4% vs 5.7%, aOR 4.78; 95% confidence interval [CI], 2.75-8.31), and persons born in a high-incidence country compared with low-incidence countries (31.0% vs 6.6%; aOR 4.19; 95% CI, 2.61-6.73). For patients with latent tuberculosis, risk of co-infection was higher among Asian (aOR 9.99; 95% CI, 5.79-17.20), or Black race/ethnicity (aOR 3.33; 95% CI, 1.78-6.23) compared with White race/ethnicity. Persons born in high-incidence countries had elevated risk of co-infection compared with persons born in low-incidence countries (aOR 2.23; 95% CI, 1.42-3.50). However, Asians or persons born in high-incidence countries were screened at similar rates to other ethnicities or persons born in low-incidence countries. ConclusionsLatent tuberculosis risk is elevated among HBV patients, and vice versa. Risk of co-infection was highest among persons born in high-incidence countries and Asians. These findings support recent guidelines to increase HBV and tuberculosis screening, particularly among persons with either infection.

S387 A Majority of Patients with Positive Multitarget-Stool DNA (mt-sDNA) Test Results Do Not Complete Follow-Up Colonoscopy: Results From a Large Urban Health System

S387 A Majority of Patients with Positive Multitarget-Stool DNA (mt-sDNA) Test Results Do Not Complete Follow-Up Colonoscopy: Results From a Large Urban Health System

Abstract PO-045: Utility of circulating tumor tissue modified viral (TTMV)-HPV DNA to resolve clinically indeterminate findings in patients following definitive treatment for HPV-driven oropharyngeal cancer

Abstract Introduction: Indeterminate results of clinical or imaging examinations are common across the care continuum, and decisions made can lead to overtreatment and psychological and financial harms for the patient. Additionally, due to the emergence of highly sensitive circulating tumor DNA assays, an indeterminate clinical status can also arise when molecular detection precedes clinical or radiological evidence of recurrence for a period of time. We recently reported &amp;gt;99% negative and &amp;gt;95% positive predictive value of circulating tumor tissue modified viral (TTMV)-HPV DNA for recurrence detection in a large, real-world cohort of patients with HPV-driven oropharyngeal cancer. Here we quantified the frequency of clinically indeterminate findings (CIF) in this patient cohort and assessed the prognostic value of TTMV-HPV DNA to resolve these CIF. Methods: This IRB-approved, retrospective observational cohort study included 543 patients across eight U.S. centers who were ≥3 months post-treatment for HPV-driven OPSCC. Patients had one or more TTMV-HPV DNA results (NavDx®, Naveris Laboratories) obtained during surveillance between February 2020 and January 2022 (n=1372 total tests), with mean follow-up time of 24 months (range: 4.9-185). Test results were correlated with physician-reported exam and imaging findings to assess disease status in follow-up. Results: Of the 543 patients, 245 patients (45.1%) had 797 CIF by imaging and/or clinical examination during their surveillance period. Of these 245 patients, 71 patients had 93 CIF that had a coincident TTMV-HPV DNA result (either negative or positive) available within 3 months of the CIF. The TTMV-HPV DNA result was able to correctly predict the presence or absence of recurrence across 91 of the 93 (97.8%) individual CIF. Both incorrectly predicted CIF were in the setting of an undetectable TTMV-HPV DNA result. One patient had their recurrence detected by chest CT 63 days later and had a positive TTMV-HPV DNA test the same day. The second patient had a positive TTMV-HPV DNA test during their subsequent immunotherapy. In contrast to the 45% of patients with CIF as a result of imaging and/or clinical examination, only 18 patients (3.3%) had CIF due to a positive TTMV-HPV DNA result that was not accompanied by clinical evidence of recurrence within 3 months. Importantly, of these 18 patients, 15 patients had confirmed recurrence at a subsequent time point (median time to recurrence: 232 days), leaving only 3 of 543 (0.6%) patients with an ongoing indeterminate recurrence status. Conclusion: Clinical indeterminate findings as a result of imaging and/or clinical examination are common, whereas clinically indeterminate status due to circulating TTMV-HPV DNA testing is rare. Our findings strongly support the clinical utility and value of monitoring circulating TTMV-HPV DNA during post-treatment surveillance to inform interpretation of indeterminate clinical findings. Citation Format: Scott Roof, Glenn Hanna, James Jabalee, Eleni Rettig, Rocco Ferrandino, Sida Chen, Marshall R. Posner, Krzysztof J. Misiukiewicz, Eric M. Genden, Raymond L. Chai, John Sims, Elaine Thrash, Scott Stern, Noah S. Kalman, Sreenija Yarlagadda, Adam Raben, Lydia Clements, Abie Mendelsohn, John M. Kaczmar, Yadav Pandey, Mihir Bhayani, Piyush Gupta, Charlotte Kuperwasser, Catherine Del Vecchio Fitz, Barry M. Berger. Utility of circulating tumor tissue modified viral (TTMV)-HPV DNA to resolve clinically indeterminate findings in patients following definitive treatment for HPV-driven oropharyngeal cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-045.

Performance of Liquid Biopsy for Diagnosis and Surveillance of Human Papillomavirus–Associated Oropharyngeal Cancer

There is growing interest in the use of circulating plasma tumor human papillomavirus (HPV) DNA for diagnosis and surveillance of patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Recent advances in the assays, combining the identification of circulating HPV tumor DNA and tumor DNA fragment analysis (tumor tissue-modified viral [TTMV]-HPV DNA), have been shown to be highly accurate. However, use of these newer techniques has been limited to small cohort studies and clinical trials. To establish the clinical efficacy of plasma TTMV-HPV DNA testing in the diagnosis and surveillance of HPV-associated OPSCC in a contemporary clinical setting. This retrospective observational cohort study included patients with OPSCC who underwent TTMV-HPV DNA testing between April 2020 and September 2022 during the course of routine clinical care. For the diagnosis cohort, patients with at least 1 TTMV-HPV DNA measurement prior to initiation of primary therapy were included. Patients were included in the surveillance cohort if they had at least 1 TTMV-HPV DNA test performed after completion of definitive or salvage therapy. Per-test performance metrics, including sensitivity, specificity, positive predictive value, and negative predictive value, for TTMV-HPV DNA testing. Of 399 patients included in the analysis, 163 were in the diagnostic cohort (median [IQR] age, 63 [56-68.5] years; 142 [87.1%] male), and 290 were in the surveillance cohort (median [IQR] age, 63 [57-70] years; 237 [81.7%] male). Of the 163 patients in the diagnostic cohort, 152 (93.3%) had HPV-associated OPSCC while 11 (6.7%) had HPV-negative OPSCC. The TTMV-HPV DNA sensitivity in pretreatment diagnosis was 91.5% (95% CI, 85.8%-95.4% [139 of 152 tests]), and the specificity was 100% (95% CI, 71.5%-100% [11 of 11 tests]). In the surveillance cohort, 591 tests conducted in 290 patients were evaluated. A total of 23 patients had molecularly confirmed pathologic recurrences. The TTMV-HPV DNA test demonstrated sensitivity of 88.4% (95% CI, 74.9%-96.1% [38 of 43 tests]) and specificity of 100% (95% CI, 99.3%-100% [548 of 548 tests]) in detecting the recurrences. Positive predictive value was 100% (95% CI, 90.7%-100% [38 of 38 tests]), and negative predictive value was 99.1% (95% CI, 97.9%-99.7% [548 of 553 tests]). The median (range) lead time from positive TTMV-HPV DNA test to pathologic confirmation was 47 (0-507) days. This cohort study demonstrated that when evaluated in a clinical setting, the TTMV-HPV DNA assay demonstrated 100% specificity in both diagnosis and surveillance. However, the sensitivity was 91.5% for the diagnosis cohort and 88.4% for the surveillance cohort, signifying that nearly 1 in 10 negative tests among patients with HPV-associated OPSCC was a false negative. Additional research is required to validate the assay's performance and, if validated, then further research into the implementation of this assay into standard clinical practice guidelines will be required.

Changes in &lt;i&gt;in vitro&lt;/i&gt; GM-CSF-exposured monocyte subset composition and phagocytic activity in children with infectious mononucleosis

The aim of the study was to investigate the features of changes in the monocytes subset composition and phagocytic activity in children with infectious mononucleosis (IM) exposed to granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. We examined 84 children aged 3 to 11 years with EpsteinBarr virus (EBV) infection diagnosed by clinical signs, positive EBV DNA test in blood lymphocytes and ELISA data (EBV-VCAIgM (+), EBV-EA-DIgG (+)). The control group consisted of 40 apparently healthy age-matched children. Monocytes were obtained by the standard method on adhesion to plastic from mononuclear cells isolated from heparinized venous blood by density gradient centrifugation. The isolated monocytes were divided into two samples: control (without GM-CSF) and experimental (50 ng of GM-CSF per 1 ml of cell suspension). The monocyte subset composition and phagocytic activity in both samples were measured by flow cytometry after 1-hour incubation at 37C ina CO2-incubator. It was found that in children with progressing IM, the blood monocyte subpopulation composition changes and their phagocytic activity is impaired. It was found that the subset composition and phagocytic activity of the blood monocytes changed in children during development of IM. Changes in the subset composition of monocytes in acute IM did not depend on the age group of children (36 and 711 years) and were characterized by increased number of pro-inflammatory (intermediate) monocytes and decreased level of anti-inflammatory (non-classical) monocytes. Features of altered monocyte phagocytic activity in children with IM depended on age. The phagocytic activity of all three monocyte subsets was reduced in children with IM 36 years old while children with IM 711 years old had reduced phagocytic activity only in intermediate and non-classical monocytes. The effect of GM-CSF in vitro on monocytes in patients with IM, regardless of the age of children, led to significantly increased level of anti-inflammatory monocytes while the phagocytic activity of cells changed less. An increase in the phagocytic number for classical monocytes after incubation with GM-CSF in vitro was noted in children with IM at the age of 36 years while the phagocytic index of this fraction of monocytes remained unchanged. The level of the phagocytic index increased only in classical monocytes of children with IM aged 711 years. The presented results determine the scientific and clinical value of studying the mechanisms of the effect of GM-CSF on cells of the immune system and prove that this cytokine can be used in a new immunotherapeutic strategy for the treatment of IM.

Estimated life-years gained and resultant cost savings from follow-up colonoscopy after a positive multi-target stool DNA (mt-sDNA) test for colorectal cancer screening in commercially insured and Medicare populations.

6642 Background: Although follow up colonoscopy (COL) after a positive stool-based colorectal cancer (CRC) screening test is necessary to complete the CRC screening process, follow-up COL rates remain suboptimal, especially among underserved populations. As of January 2023, federal policies require commercial insurers and Medicare to eliminate out of pocket costs for follow-up COL. To estimate the implications of this policy change, we compared the clinical and fiscal outcomes for a simulated cohort receiving a follow-up COL after a non-invasive CRC test ($0 cost sharing), compared to the same cohort not completing follow-up COL (status quo). Methods: Using the validated CRC-AIM model, we simulated a cohort of 6 million average-risk individuals who received mt-sDNA (commercial patients at age 45 and Medicare patients at age 65) and further analyzed only the population with positive mt-sDNA. Life-years gained, CRC incidence, CRC-related mortality and total costs of care (inclusive of CRC screening and treatment) were calculated for a cohort that underwent follow-up COL and compared these outcomes to that same cohort that did not complete follow-up COL. The cost of follow-up COL was assumed to be $1,576 for Medicare and $3,086 for commercially insured patients ($0 out of pocket costs for all). Results: Patients undergoing follow-up COL after a positive mt-sDNA experienced more life-years (83 per 1,000 commercially insured patients and 80 per 1,000 Medicare beneficiaries) compared to those who did not undergo follow-up COL. The follow-up COL resulted in reductions in CRC incidence and CRC mortality by 14% and 16% for commercial and 19% and 23% for Medicare beneficiaries, respectively. Compared to those patients with a mt-sDNA positive test result and did not complete follow-up COL, the total cost per patient for those receiving follow-up COL was $3,339 less for commercially insured ($15,690 – no follow up vs. $12,351 – follow up) and $4,382 less for Medicare beneficiaries ($19,337 – no follow up vs. $14,955 – follow up). Total spending for patients receiving follow-up COL was cost-saving when compared to no follow-up as long as the COL costs were less than $6,269 for commercial plans and $5,753 for Medicare. Conclusions: Completing a follow-up COL after a positive mt-sDNA screening saves lives, enhances equity, and lowers total expenditures. Thus, health care stakeholders should invest in efforts to identify and reduce barriers that ultimately lead to an increase uptake of this potentially lifesaving and cost-reducing intervention.

Abstract 3360: Negative predictive value of circulating tumor tissue modified viral HPV DNA for identifying recurrence among patients treated for HPV-driven oropharyngeal cancer

Abstract Purpose: Despite favorable outcomes, up to 20% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will experience recurrence. Monitoring circulating tumor tissue modified viral (TTMV)-HPV DNA during post-treatment surveillance has emerged as a tool that has demonstrated &amp;gt;95% positive predictive value (PPV) for detecting recurrence. Here we describe a large real-world population with detailed clinical follow-up, permitting determination of the longitudinal negative predictive value (NPV) of the assay. Patients and methods: This IRB-approved, retrospective observational cohort study included 312 patients across five U.S. centers who were ≥3 months post-treatment for HPV-driven OPSCC. Patients had one or more TTMV-HPV DNA results (NavDx®, Naveris Laboratories) obtained during surveillance between February 2020 and January 2021. A baseline TTMV-HPV DNA test was not required. HPV status was assessed by p16 immunohistochemistry or HPV PCR/ISH. Test results were correlated with physician-reported exam and imaging findings to assess disease status in follow-up. Results: The cohort was mostly male (85%), had a median age of 61 (range: 27-81), included smokers (50%), and 282 (90%) had involved nodes (N1: 204, N2: 70, N3: 8) at initial staging. Curative-intent treatment involved surgery with or without another modality in 54% of cases (169/312). Median follow-up time was 23.5 months, and 39 patients (12.5%) had documented recurrence. Most patients had &amp;gt;1 TTMV-HPV DNA test result ≥3 months post-treatment (231, 74%), with 48 (15%) having 5 or more tests. Among patients with multiple negative surveillance tests, the median time between tests was 126 days (4.2 months, range: 0.37-24.2). The first TTMV-HPV DNA surveillance test was most often performed within the first year post-treatment (195, 63%). Across 812 test results, the NPV was 99.5%. There were 4 false negative tests among patients with confirmed p16-positive (3/4) or HPV PCR-positive (1/4) biopsy-proven recurrence. One of these patients had a subsequent positive TTMV-HPV DNA test during salvage immunotherapy. Only one of these patients had baseline TTMV-HPV DNA testing available, which showed a low positive &amp;lt;50 TTMV-HPV16 DNA Score, whereas the other three patients did not have a baseline result available. Conclusion: Our findings further support the clinical potential of monitoring circulating TTMV-HPV DNA during post-treatment surveillance. We demonstrate a very high assay NPV correlated with physician-reported outcomes. TTMV-HPV DNA can be used to assist in surveillance and could inform imaging needs and future practice guidelines for HPV-driven head and neck cancer survivors. Citation Format: Glenn J. Hanna, Scott Roof, James Jabalee, Eleni M. Rettig, Rocco M. Ferrandino, Sida Chen, Marshall Posner, Krzysztof J. Misiukiewicz, Eric M. Genden, Raymond L. Chai, John Sims, Elaine Thrash, Scott J. Stern, Adam Raben, Lydia I. Clements, Abie H. Mendelsohn, Charlotte Kuperwasser, Catherine Del Vecchio Fitz, Barry M. Berger. Negative predictive value of circulating tumor tissue modified viral HPV DNA for identifying recurrence among patients treated for HPV-driven oropharyngeal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3360.

S329 Comparison of the Effect of a Positive Stool DNA Test on Mucosal Inspection Time to Average Risk Screening Colonoscopy

S329 Comparison of the Effect of a Positive Stool DNA Test on Mucosal Inspection Time to Average Risk Screening Colonoscopy

The Incidence of Positive Visual Inspection of Acetic Acid in Dr Cipto Mangunkusumo General Hospital Followed by Liquid Based Cytology, HPV testing and Colposcopy: A Cross Sectional Study

Introduction : Cervical cancer is most common cancer in women in Asia Oceania and worldwide. VIA(Visual Inspection after Acetic acid) is being used as an alternative in low- and middle-income countries due to the minimal equipment required. Data from recent systematic reviews and multicentre trials show that VIA to be moderately sensitive for precancerous lesions, as compared with Pap testing. This study aim to determine the incidence of positive VIA, LBC, HPV DNA testing and colposcopy findings obtained from positive VIA cases in Dr. Cipto Mangunkusumo General Hospital.Methods: This was a cross-sectional study. Data was collected from cervical cancer screening by VIA examination at Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia in 2017. Age, VIA results were recorded. The results showed abnormal and predictive cancer lesions (acetowhite lesion) were defined as a “positive test.” The positive VIA result followed by LBC, HPV DNA testing, and Colposcopy. Only 25 performed LBC and HPV DNA test, and 30 of the VIA positive were performed Colposcopy. Results: A total of 1.960 subjects were recruited for this study. The mean age of the subjects was 34.5 years, and 908 (46 %) subjects belong to the 30-40 years age group. Negative VIA result were found in 1893 subjects (96,58%) and 67 subjects (3,42%) had positive results. From 25 VIA positive subject whose gone through LBC and HPV test, 9 subjects (36%) had abnormal LBC, 3 subjects (12%) had positive HPV DNA test. From 30 positive VIA whose got colposcopy examination 17 subjects (56,6 %) had abnormal colposcopy.Conclusions: The number of VIA screening participants in RSCM, Jakarta, Indonesia with positive VIA results is low. Further studies regarding the validation of VIA are required to evaluate its diagnostic value.

Efficacy of Oral Zinc Sulfate Supplementation on Clearance of Cervical Human Papillomavirus (HPV); A Randomized Controlled Clinical Trial.

Aim:Human Papillomavirus is one of the most crucial infectious disease in gynecology disease. To assess the efficacy of supplemental zinc treatment in clearance of HPV infection. Methods:Eighty zinc-sufficient women between 21-55 years, with positive HPV DNA testing, and abnormal cervical cytology in Pap test (ASCUS or LISL) were randomly divided to case (n=40) and control group (n=40). Case group received oral tablets of zinc sulfate twice a day for 3 months while control group received no placebo. During follow-up patients underwent repeat HPV DNA test and PAP test and were evaluated for clearance/persistence of HPV infection and regression/progression in the lesion grading. Results:As far as demographics, serum zinc levels and the relevant risk factors for persistence of HPV were concerned, there was no significant difference between two groups, except for the frequency distribution of HR-HPV which was significantly higher in case group. Zinc treatment for 3 months reduced the risk of persistence of HPV infection and progression from baseline cytology (OR = 0.130) (CI 95% 0.04-0.381; p <0.001) and 0.301 (95% CI 0.777-0.116; p = 0.012), respectively. Age, initial cytology, HPV type, and contraceptive method were not related to persistence of HPV. Serum zinc levels increased in the casr group as a result of oral zinc consumption for 3-month period, though without any statistical significance (p = 0.407). Conclusion:The results of the following study suggested that oral intake of zinc sulfate supplement for 3 months increases the rates of HPV clearance and resolution of pre-existing cervical lesion.

Comparison of cytopathologic findings in patients with negative Pap test and positive high-risk HPV infection among three groups.

Comparison of colposcopy-guided biopsy and endocervical cytologic (ECC) results in patients with negative Papanicolaou (Pap) and positive high-risk (HR) HPV tests in the three groups of HPV 16/18, non-16/18 HR-HPV (other HR-HPV), and concurrent infection of either HPV 16/18 and at least one subtype of other HR-HPVs. This cross-sectional study was conducted among women aged 30-65 who had negative Pap and positive HR-HPV DNA tests. Pap test was performed using liquid cytology. For HPV DNA testing, the polymerase chain reaction (PCR) method was used. Among 394 participants, 111 (28.2%) were in the HPV 16/18, 226 (57.4%) in the Other HR-HPV, and 57 (14.4%) in the concurrent group. The mean age of participants was 35.71 ± 7.1years. Cervical intraepithelial neoplasia (CIN) grade 2/3 were seen in 29 (26.1%) patients of HPV 16/18, 60 (26.5%) of other HR-HPV, and 18 (31.6%) of concurrent infection group (P = 0.593). HPV 52 was the most common subtype in the other HR-HPV group (15%). The risk of high-grade CIN lesions in patients with negative Pap test and positive other HR-HPV was not significantly less than patients with positive HPV 16/18. Besides, the risk of losing the patients to 1-year follow-up seems high.

The Influence of Sexual Behavior and Demographic Characteristics in the Expression of HPV-Related Biomarkers in a Colposcopy Population of Reproductive Age Greek Women.

Simple SummaryThis observational study aimed to investigate the possible influence of sexual behavior and demographic characteristics in the expression of HPV-related biomarkers in a colposcopy population. Lifestyle factors that impacted HPV DNA positivity in a statistically significant manner were younger age at first sexual intercourse, a history of more than four sexual partners as well as a partner change during the last year before HPV DNA assessment. Although ambitious, the development and validation of lifestyle scoring systems that combine molecular and epidemiological patient data to effectively predict underlying cervical pathology will represent a milestone in the quest of cervical cancer prevention.Despite the significant scientific evolution in primary and secondary cervical cancer prevention in the battle started by George Papanicolaou in the previous century, global cervical cancer mortality rates remain disappointing. The widespread implementation of HPV-related molecular markers has paved the way to tremendous developments in cervical cancer screening, with the transition from cytological approach to the more accurate and cost-effective HPV testing modalities. However, the academic audience and different health systems have not yet adopted a universal approach in screening strategies, and even artificial intelligence modalities have been utilized from the multidisciplinary scientific armamentarium. Combination algorithms, scoring systems as well as artificial intelligent models have been so far proposed for cervical screening and management. The impact of sexual lifestyle inherently possesses a key role in the prevalence of HPV-related biomarkers. This study aimed to investigate any possible influence of sexual behavior and demographic characteristics in the expression of HPV-related biomarkers in a colposcopy population from October 2016 to June 2017, and corroborated the determining role of age at fist intercourse; the older the age, the lower the probability for DNA positivity. Multivariate analysis illustrated additionally that a number of sexual partners exceeding 4.2 was crucial, with women with ≤5 partners being approximately four times less likely to harbor a positive HPV DNA test (p < 0.0001). Similarly, a reported partner change during the last year before HPV DNA assessment contributed to 2.5 times higher odds for DNA positivity (p = 0.0006). From this perspective, the further development and validation of scoring systems quantifying lifestyle factors that could reflect cervical precancer risk seems paramount.

Prenatal hepatitis B screening, and hepatitis B burden among children, in Ontario: a descriptive study.

Ontario is 1 of 5 provinces that immunize adolescents for hepatitis B virus (HBV), despite the World Health Organization recommendation for universal birth dose vaccination. One rationale for not vaccinating at birth is that universal prenatal screening and related interventions prevent vertical transmission. The aims of our study were to evaluate the uptake and epidemiology of prenatal HBV screening, and to determine the number of children in Ontario with a diagnosis of HBV before adolescent vaccination. We extracted data from ICES, Public Health Ontario and Better Outcomes & Registry Network (BORN) Ontario databases. We assessed prenatal screening uptake and prevalence of prenatal hepatitis B surface antigen (HBsAg) from 2012 to 2016, as well as subsequent hepatitis B e-antigen (HBeAg) and HBV DNA testing and percent positivity. We used age and region to subcategorize the results. In a separate unlinked analysis, we evaluated the number of children positive for HBV aged 0-11 years who were born in Ontario from 2003 to 2013. From 2012 to 2016, 93% of pregnant women were screened for HBV, with an HBsAg prevalence of 0.6%. Prevalence of HBsAg increased with age, peaking at older than 45 years at 3%. North Toronto had the highest overall prevalence of 1.5%, whereas northern Ontario had the lowest. Of women who were HBsAg positive, HBeAg and HBV DNA tests were subsequently ordered in 13% and 38%, respectively. Of children born in Ontario between 2003 and 2013, 139 of 23 759 tested positive for HBV. Prenatal HBV screening is not universal and subsequent evaluation is poor, limiting optimal intervention and possibly contributing to some Ontario-born children being given a diagnosis of HBV before age 12 years. These findings underscore the limitations of the province's adolescent vaccination strategy.

CyclinA1 Promoter Methylation in Self-Sampling Test.

Background:Self sampled HPV testing is a cervical cancer screening method . However, cytology in self-sampled specimen cannot be used as a triage test. Therefore, other methods for triage should be considered. CyclinA1 (CCNA1) promoter methylation has strong association with cervical precancerous and cancerous lesion. The objective of this study was to compare the diagnostic value of CCNA1 and self-sampled specimen for detecting high-grade cervical intraepithelial lesions or worse (CIN2+). Materials and Methods:A cross sectional study was conducted. Women with abnormal cytology or positive for high risk HPV (hrHPV) indicated for colposcopic examination were enrolled. Self-collected sampling for hrHPV DNA (SS-HPV) and CCNA1 were performed. hrHPV DNA testing was done by Cobas 4800 method. CCNA1 promoter methylation was detected by CCNA1 duplex methylation specific PCR. Histopathologic result as CIN2+ obtaining from colposcopic directed biopsy or excisional procedure was considered as positive a gold standard. The results of hrHPV and CCNA1 were reported as positive or negative. Sensitivity specificity, positive predictive value, and negative predictive value of SS-HPV and CCNA1 were calculated by comparing the results with the gold standard. Results:Two hundreds and eighty women were recruited. High-grade cervical lesions and cervical cancer (CIN2+) were diagnosed in 21.8% (61 cases) of the patients. The most common type of hrHPV was non 16, 18 subtype, followed by HPV16 and 18. CCNA1 was positive in 13 patients out of whom, twelve were CIN2+. Sensitivity of CCNA1 was 19.7 % and its specificity and accuracy were 99.5% and 82.14%, respectively. The sensitivity of SS-HPV was 70.5%, and its specificity and accuracy were 39.2% and 43.3%, respectively. Conclusion: Due to high specificity and positive predictive value of CCNA1, it can be used as alarming sign of having high-grade cervical intraepithelial lesions, especially in patient who has positive hrHPV DNA test based on self-collected sampling.