Timothy G. Ramseyer MD, Bethany Batson MD, Daisy Wu MD, Jonee L. Matsko SCT, MB, Amy K. Colaizzi SCT, Samer N. Khader MD, Chengquan Zhao MD
{"title":"Pap testing and high-risk HPV testing for women aged 65 years and older with surgical pathology follow-up","authors":"Timothy G. Ramseyer MD, Bethany Batson MD, Daisy Wu MD, Jonee L. Matsko SCT, MB, Amy K. Colaizzi SCT, Samer N. Khader MD, Chengquan Zhao MD","doi":"10.1002/cncy.70111","DOIUrl":"10.1002/cncy.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Current professional guidelines recommend discontinuing Papanicolaou (Pap) test screening in women aged 65 years and older who have had adequate prior negative testing. However, limited data exist on Pap test performance and histologic outcomes in this population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Searches were performed for all Pap tests from women aged 65 years and older accessioned at a women’s hospital between January 2023 and December 2024. Pap tests were performed using the liquid-based cytology ThinPrep test, and high-risk HPV testing was performed using Aptima high-risk human papillomavirus (HPV) assays. Surgical pathology follow-up within 6 months was recorded. A Pearson χ<sup>2</sup> test was performed to compare HPV positivity among patients who had abnormal Pap tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 1536 women aged 65 years and older underwent Pap testing during the study period. The overall HPV-positivity rate was 24.2%. Abnormal Pap results (atypical squamous cells of undetermined significance or worse) comprised 939 of 1536 cases (61.1%). Histologic follow-up was available for 402 cases. Lesions categorized as cervical intraepithelial neoplasia grade 2 (CIN2) or more severe disease were identified in 94 cases (23.3%), including 11 squamous cell carcinomas, three endocervical carcinomas, 40 CIN2/3 lesions, and 40 endometrial carcinomas. Notably, three of 11 squamous cell carcinomas (27.3%) and 12 of 40 CIN2/3 lesions (30%) were HPV-negative.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The abnormal Pap rate in women aged 65 years and older was high (61.1%), whereas HPV positivity remained low. CIN2 or more severe disease and endometrial lesions after negative HPV testing occurred at a substantial rate (33.8%). The rate for detecting atypical glandular cells was also elevated (3.0%), correlating with a significant number of endometrial carcinoma diagnoses. These findings underscore the need for additional research and suggest that continued screening with Pap and HPV cotesting may benefit older women.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Funding cuts and mixed messages threaten the rise of mRNA vaccine technology","authors":"Bryn Nelson PhD, William Faquin MD, PhD","doi":"10.1002/cncy.70096","DOIUrl":"10.1002/cncy.70096","url":null,"abstract":"<p>In the United Kingdom, researchers are gearing up for a potentially “game-changing” trial of a messenger RNA (mRNA) vaccine that treats head and neck cancers. In the United States, scientists found that mRNA-based COVID-19 vaccines boosted the tumor-fighting effects of immunotherapy so significantly that they are floating the idea of a universal cancer vaccine.</p><p>Although mRNA technology is still in its early days, medical researchers have expressed growing optimism that it will not only yield effective vaccines against a long list of infectious diseases but also help the body’s immune system to kill off cancerous cells. The Nobel Prize–winning science is based on the discovery that chemically modifying the bases in mRNA tamps down the inflammation observed with unmodified mRNA while ramping up its protein production. Those changes allow the genetic template to quickly—and more safely—direct the mass production of vaccine targets that elicit strong immune responses.</p><p>The mRNA vaccine platform is widely credited as the key breakthrough enabling COVID-19 vaccines to be developed in less than a year under the public–private venture dubbed Operation Warp Speed during the first administration of President Donald Trump. Conservative estimates suggested that globally, the vaccines saved at least 2.5 million lives during the pandemic.<span><sup>1</sup></span></p><p>Five years later, however, the same disease-preventing technology has been assailed by the second Trump administration and Department of Health and Human Services (HHS) Secretary Robert F. Kennedy, Jr., even as the HHS has supported its use for cancer applications. Amid the mixed messages and contradictions, concerned scientists are warning that the new hostility toward mRNA technology could harm fledgling efforts to treat a wide range of cancers as well.</p><p>In an August 5, 2025, press release, HHS announced that it was terminating 22 mRNA vaccine development initiatives worth nearly $500 million. Nor would the department initiate any new mRNA-based projects, as Kennedy asserted that HHS was “moving beyond the limitations of mRNA and investing in better solutions.”<span><sup>2</sup></span> In response to an inquiry by <i>CytoSource</i>, HHS spokesperson Emily G. Hilliard did not specify to what limitations Kennedy was referring. As to whether he would continue supporting mRNA technology focused on cancer therapeutics, however, she pointed to a <i>Wall Street Journal</i> article describing a new $200 million HHS-backed initiative that will conduct clinical trials of vaccines aimed at preventing cancer recurrence.<span><sup>3</sup></span></p><p>That support has created a striking contrast with Kennedy’s disdain for the technology when applied to infectious diseases. In the HHS press release, he claimed that “the data show these vaccines fail to protect effectively against upper respiratory infections like COVID and flu.” His quote was linked to a 181-page bibliography entitled “CO","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Azad MBBS, Timothy E. Graham MD, Shiri Levy MD, Evana Velanzuela-Sheker MD, David Bimston MD, Andrea Ferenczi MD, Yang Chen PhD, Mohammed Alshalalfa PhD, Yangyang Hao PhD, Joshua P. Klopper MD, Richard T. Kloos MD, Anupam Kotwal MD
{"title":"Analysis of PLEKHS1 promoter mutation in preoperative thyroid nodule samples","authors":"Sarah Azad MBBS, Timothy E. Graham MD, Shiri Levy MD, Evana Velanzuela-Sheker MD, David Bimston MD, Andrea Ferenczi MD, Yang Chen PhD, Mohammed Alshalalfa PhD, Yangyang Hao PhD, Joshua P. Klopper MD, Richard T. Kloos MD, Anupam Kotwal MD","doi":"10.1002/cncy.70103","DOIUrl":"10.1002/cncy.70103","url":null,"abstract":"<p>Indeterminate thyroid nodules carry a wide range of malignancy prevalence, necessitating incorporation of molecular testing to guide management. Molecular test results help guide prognosis to a certain extent, but additional prognostic factors need to be identified. Limited data have linked <i>PLEKHS1</i> promoter (<i>PLEKHS1p</i>) mutations with higher aggressiveness of thyroid cancer. Hence, we aimed to evaluate the diagnostic and prognostic value of <i>PLEKHS1p</i> mutations in preoperative thyroid nodules undergoing molecular testing. We assessed <i>PLEKHS1p</i> mutations in 9279 patient samples from April 2023 to June 2024 among indeterminate thyroid nodules ((B)ethesda III/IV) with Afirma GSC-(S)uspicious results as well as among B V/VI cytology thyroid nodules. We also analyzed a subset of 20 consecutive cases positive for <i>PLEKHS1p</i> mutations with surgical resection for histology and for co-occurring molecular alterations from the Afirma testing. <i>PLEKHS1p</i> mutations were positive in 60/9279 (0.6%) of patient samples with three times higher frequency in B VI compared to B III cytology nodules (1.36% vs 0.47%, <i>p</i> < .01). Among the 60 samples harboring <i>PLEKHS1p</i> mutations, 28 had the C593T hotspot mutation, 38 the G590A mutation, and six samples had both; four samples had concomitant <i>TERTp</i> mutations and 18 samples had concomitant <i>BRAFp.V600E</i> alterations. Our study demonstrated an overall low frequency of <i>PLEKHS1p</i> mutations, but this frequency was highest among malignant (B VI) cytology thyroid nodules. The frequency of <i>PLEKHS1p</i> mutations did not strongly correlate with the severity of thyroid cancer but the surgical sample size was limited. Further research is needed to clarify the role of <i>PLEKHS1p</i> mutations in thyroid nodules and cancer.</p>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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