Cervical cancer screening has reduced the incidence of cervical cancer over the past 75 years. The primary aim of this study was to determine if women receiving Gardasil™ (HPV4 vaccine) participated in future cervical cancer screening at the same rate as that observed for unvaccinated women matched on birth year and health care campus. This is a retrospective cohort study of subjects selected from 27,786 females born from 1980 to 1992 who received health care in the Truman Medical Center safety net health system in Kansas City Missouri, USA. 1154 women 14–26 years old who received at least one dose of HPV4 vaccine between 2006 and 2009 were chosen at random from the vaccine records. 1154 randomly chosen unvaccinated women were age and health campus matched to the vaccinated women and all were followed until July 1, 2013. Women who were screened after 21 years and received three vaccine doses before 21 years, had the lowest screening rate of 24%. Their only predictive factor for screening, compared to the unvaccinated, was being closer to 21 years than 14 years at vaccination (aOR = 1.71 95% CI: 1.45, 2.00). Women vaccinated with three doses and screened at or after 21 years had the highest screening rate of 84% predicting a six-fold increase in screening participation over no vaccine received (aOR = 5.94 95% CI: 3.77, 9.35). Our results suggest that women who receive HPV4 vaccination closer to 21 years, not 14, are more likely to participate in cervical cancer screening in an underserved US population.
Objectives Mucinous cystic neoplasm of the liver is characterized by neoplastic mucinous and/or biliary epithelium surrounded by ovarian-type stroma. Immunohistochemical studies have shown that the ovarian-type stroma expresses estrogen receptor, suggesting potential hormonal responsiveness. The molecular biology of mucinous cystic neoplasm of the liver remains poorly studied. Methods Transcriptome sequencing and immunohistochemistry were performed on a series of mucinous cystic neoplasms. Results Mucinous cystic neoplasm of the liver exhibited significantly increased RNA expression of ovarian stromal markers WT1, PR, and ER2 and sex cord stromal markers SF-1, inhibin-α, and calretinin compared with nonneoplastic liver. Immunohistochemistry confirmed the RNA-level data. Evidence for sex hormone biosynthesis was identified by significant overexpression of multiple estrogen biosynthetic enzymes. Expression of 17β-hydroxysteroid dehydrogenase 1 was confirmed immunohistochemically. Pathway analysis also identified significant upregulation of the hedgehog and Wnt pathways and significant downregulation of T-helper 1 and T-helper 2 pathways. Conclusions Mucinous cystic neoplasm of the liver recapitulates ovarian stroma at the morphologic, DNA, RNA, and protein levels. These data support the concept that this tumor likely arises from ectopic primitive gonadal tissue and/or stromal cells with capacity to transdifferentiate to ovarian cortical cells.
Objectives Steatohepatitic hepatocellular carcinoma is a distinct variant of hepatocellular carcinoma strongly associated with underlying nonalcoholic steatohepatitis. The molecular biology of steatohepatitic hepatocellular carcinoma is not fully elucidated, and thus we aimed to investigate the molecular underpinnings of this entity. Methods Transcriptomic analysis using RNAseq was performed on eight tumor-nonneoplastic pairs of steatohepatitic hepatocellular carcinoma with comparison to conventional hepatocellular carcinoma transcriptomes curated in The Cancer Genome Atlas. Immunohistochemistry was used to validate key RNA-level findings. Results Steatohepatitic hepatocellular carcinoma demonstrated a distinctive differential gene expression profile compared with The Cancer Genome Atlas curated conventional hepatocellular carcinomas (n = 360 cases), indicating the distinctive steatohepatitic hepatocellular carcinoma morphology is associated with a unique gene expression profile. Pathway analysis comparing tumor-nonneoplastic pairs revealed significant upregulation of the hedgehog pathway based on GLI1 overexpression and significant downregulation of carnitine palmitoyltransferase 2 transcript. Glutamine synthetase transcript was significantly upregulated, and fatty acid binding protein 1 transcript was significantly downregulated and immunohistochemically confirmed, indicating steatohepatitic hepatocellular carcinoma tumor cells display a zone 3 phenotype. Conclusions Steatohepatitic hepatocellular carcinoma demonstrates a distinctive morphology and gene expression profile, phenotype of zone 3 hepatocytes, and activation of the hedgehog pathway and repression of carnitine palmitoyltransferase 2, which may be important in tumorigenesis.
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