Aberrant promoter methylation analysis on exfoliated cell samples is a potential diagnostic tool for cervical cancer screening that potentially may be used alone or in conjunction with cytology and/or human papillomavirus testing.

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We developed a liquid bead microarray (LBMA) assay for genotyping genital human papillomaviruses (HPVs) based on the MY09-MY11-HMB01 PCR system and the reverse line blot (RLB) assay probe sequences. Using individual HPV plasmids, we were able to detect as few as 50 copies per reaction. In two separate retrospective studies, the LBMA assay was compared to the RLB assay and to the Hybrid Capture II (hc2) assay. Testing was performed without knowledge of other assay results. In the first study, 614 cervical swab samples (enriched for HPV infection) from 160 young women were tested for HPV DNA, and 360 (74.8%) type-specific HPV infections were detected by both assays, 71 (14.8%) by the LBMA assay only, and 50 (10.4%) by the RLB assay only. to 100%], respectively). The percentages of negative results among 398 women without >CIN2were similar for the LBMA and hc2 assays (45% and 50%, respectively). The repeat test reproducibility for 100 samples was 99.1% (kappa ‫؍‬ 0.92; 95% CI, 0.90 to 0.95). We conclude that the new LBMA assay will be useful for clinical and epidemiological research.Human papillomavirus (HPV) is the central etiological agent for virtually all cervical cancers, for a substantial proportion of other anogenital tract cancers, and for a smaller proportion of head and neck cancers (3, 20). Currently, more than 100 different HPV types have been identified, and at least 40 types infect the anogenital epithelium. The risk of cancer is not the same for all HPV types. High-risk HPV types include HPV type 16 (HPV-16) and , and -CP6108. Potentially high-risk types include 21). HPV DNA testing has been used (i) for triage of women with a Papanicolaou (Pap) test finding of atypical squamous cells of undetermined significance (ASC-US), (ii) for monitoring for recurrence of a precancerous cervical lesion or cancer after treatment, and (iii) as a primary screening method for cervical cancer in women 30 years old and older (1, 23, 31).The only FDA-approved HPV assay for clinical testing, the Hybrid Capture II (hc2) assay, distinguishes high-risk HPVs from low-risk HPVs but does not provide individual HPV genotyping information. HPV type-specific assays are likely to have a role in the clinical management of the neoplastic diseases associated with HPV infection. Although 60 to 70% of U.S. women become infected with one or more high-risk genital types of HPV during their lifetime, most infections are quickly resolved and without consequence (2,6,19). Women who remain persistently positive for the same high-risk HPV type for extended periods are at increased risk for progression to cancer (11,12). HPV genotyping is needed to differentiate women who are repeatedly positive for the same high-risk HPV type from those who are simply sequentially infected with different high-risk types of HPV. As the use of prophylactic HPV vaccines becomes more widespread, surveillance for population-level effectiveness will become an increasingly important activity that is likely to require the use of an HPV type-specific assay (10,27). ...

African American cancer patients have higher mortality rates and shorter survival times compared with European American patients (1-5). In the United States, for every 100,000 cancer patients, the age-adjusted cancer-associated mortality for African American versus European American patients was 189.54 and 163.54 respectively, resulting in a disparity ratio of 13.87 % (2-5). When examined for individual tumor types, the disparity in mortality was higher in African American patients for cancers of the breast, colon, rectum, uterus, liver, lung, bronchus, and prostate with disparity ratios ranging from 6.41% (for lung cancer across both sexual phenotypes) to 118.52 % (for men with prostate cancer [PCa]). This observation is consistent with the 5-and 10-year survival data obtained from the Surveillance Epidemiology and End Results database (Supplemental Table 1; supplemental material available online with this article; BACKGROUND. African American patients have higher cancer mortality rates and shorter survival times compared with European American patients. Despite a significant focus on socioeconomic factors, recent findings strongly argue the existence of biological factors driving this disparity. Most of these factors have been described in a cancer-type specific context rather than a pan-cancer setting.

p16 INK4a , a cell cycle regulation protein, accumulates in abnormal epithelial cells infected with high-risk human papilloma virus (HPV). In immunostaining studies, p16 INK4a has shown potential as a marker of high grade cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. To evaluate its potential use in cervical cancer screening, we conducted a feasibility study to compare the performance of a new enzyme linked immunosorbant assay (ELISA) for p16 INK4a (mtm laboratories, Heidelberg, Germany) to that of the Hybrid capture 2 TM (hc2) test for high-risk HPV DNA for the detection of CIN3. Three hundred and nineteen women were referred from Western Washington Planned Parenthood clinics for colposcopy examination and cervical biopsy because of abnormal Pap test results. Cervical samples were obtained from study participants for p16 INK4a ELISA, liquidbased cytology and hc2. The order (first and second) for obtaining samples for cervical cytology and p16 INK4a ELISA changed with every other subject. Concentrations of p16 INK4a protein were higher when the sample was taken before the cytology. The sensitivity of p16 INK4a ELISA (concentration 8 units/ml) taken as first sample was 90.0% for CIN3, and the sensitivity of HC2 taken as a second sample was 85%. In the same group, the specificity of p16 INK4a ELISA (46.9%) was slightly better than hc2 (35.4%) Results from this proof-of-concept study suggest that p16 INK4a ELISA has a similar sensitivity and slightly better specificity for CIN3 compared to hc2. These findings support proceeding with a larger study with samples from a population of women presenting for routine cytology screening. ' 2007 Wiley-Liss, Inc.Key words: p16 INK4a ; ELISA; CIN; screening; HPV The Pap smear has been an effective screening tool for cervical cancer, but it is limited with respect to its sensitivity, cost and requirement of significant infrastructure and technology to be effective. Human papillomavirus (HPV) testing has been proposed as a possible screening tool in resource poor settings where Pap screening is not feasible; however testing for high-risk HPV deoxyribonucleic acid (DNA) is limited by its poor specificity. 1 The search for specific biomarkers of HPV infected precancerous cells has yielded a number of possible markers of disease, including p16 INK4a .p16 INK4a is a protein involved in cell cycle regulation and accumulates in abnormal epithelial cells infected with high-risk HPV. p16 INK4a is a cyclin dependent kinase (CDK) inhibitor that regulates the activity of CDK4 and CDK6. It is inactivated in many cancers by genetic deletion or hypermethylation. 2 In non-HPV associated tumors, this inactivation leads to increased CDK activity and inactivation of the retinoblastoma protein (pRb), resulting in disruption of the cell cycle and increased cell proliferation. However, in HPV-associated tumors, inactivation of pRb by highrisk HPV oncoprotein E7 leads to cell proliferation and markedly increased levels of p16 INK4a . Staining of histology and cytology ...

This paper presents a 5-year follow-up of a randomized, controlled trial, which compared microwave endometrial ablation (MEA) with transcervical resection of the endometrium (TCRE) for women with heavy menstrual bleeding. Two hundred sixty-three women were randomized to receive either MEA (n ϭ 129) or TCRE (n ϭ 134). For the current study, participants who were at least 60 months postprocedure were sent a questionnaire concerning satisfaction with and acceptability of their treatment method, menstrual status, changes in health-related quality of life, and any further surgery received. This was the same questionnaire that had been sent at 1-and 2-years of follow-up.Two hundred thirty-six of the original 263 study participants (90%) returned a completed questionnaire, including 116 MEA patients and 120 TCRE patients. Total or general satisfaction was reported by significantly more of those who underwent MEA compared with those who had TCRE (86% vs. 74%). Similarly, 83% and 75%, respectively, reported a cure or acceptable improvement in their symptoms, 97% and 91% expressed overall treatment acceptance, and 97% and 89% said that they would recommend the procedure to a friend. Both groups had similar, significant improvement in bleeding and pain scores, and 96% overall reported amenorrhea or lighter periods. Significantly more women in the TCRE group experienced dyspareunia compared with the MEA group (11% vs. 6%, respectively). Premenstrual symptoms improved significantly for both groups.Quality-of-life scores were improved for all participants. Disruptions to work or leisure activities were significantly lower in both treatment groups.In all, 24% of the patients who had MEA and 28% of those who had TCRE had undergone further gynecologic surgery in the follow-up period. This includes a 16% hysterectomy rate for the MEA cohort and 25% hysterectomy rate for women who had TCRE. Nearly all of the 20 hysterectomies among women in the MEA arm occurred within 24 months of the initial procedure. Reasons for hysterectomy were bleeding, combined bleeding and dysmenorrhea, cyclic pain, and miscellaneous conditions, including 1 woman in the TCRE arm who was operated on for endometrial carcinoma. GYNECOLOGY Volume 60, Number 7 OBSTETRICAL AND GYNECOLOGICAL SURVEY ABSTRACT The authors performed a medical chart review of all women diagnosed with atypical squamous cells of undetermined significance (ASCUS) between July 2002 and February 2004 to determine the presence of oncogenic human papillomavirus (HPV) according to patient age. Other risk factors were also noted. Cervical smears were evaluated using fluid-based thin-layer cytology (PreservCyt; Cytyc Corp., Marlborough, MA). Office Gynecology 435 436 Obstetrical and Gynecological Survey ABSTRACT This paper presents a series of 970 women who reported to the Chronic Pelvic Pain Clinic at the University of North Carolina between July 1993 and December 2000 with pelvic pain of at least 6 months duration. The authors investigated the prevalence of irritable bowel syndrome (IBS) in th...

As an adjunct test to colposcopy, liquid cytology was similar to conventional cytology. Given current practice patterns, repeated liquid cytology at the time of colposcopy is rarely clinically useful.

Breast cancer (BCa) is a disease that affects over a quarter million women in the US every year. Our laboratory studies reprogrammed energy metabolism in BCa, which is an essential hallmark of the disease. Specifically, we focus on the metabolic rewiring events that occur in BCa, intending to identify cancer-associated metabolic vulnerabilities to treat this aggressive disease. Using a global metabolic profiling approach, we have determined that the metabolite N-acetylaspartate (NAA) is highly accumulated in patients with BCa. Prior studies involving NAA in other cancer types have attributed its accumulation to the upregulation of the enzyme N-acetyl transferase (NAT8L), which synthesizes NAA. However, using matched gene expression data, we found that the accumulation of NAA in these BCa tumors rather coincides with the downregulation of aspartoacylase (ASPA), the enzyme that breaks down NAA. To determine the role of NAA in BCa progression, we generated multiple cell line models containing either NAT8L knockdown, ASPA overexpression, or a combination of the two in the cell line MDA-MB231 in a bid to deplete intracellular NAA. We used these models to test for metastasis by tail vein injection in immunocompromised mice. Consistent with our expectations and other reports, NAT8L knockdown resulted in reduced lung metastasis. Interestingly, however, NAA depletion via ASPA overexpression increased metastasis to the lung in vivo. Furthermore, the combination of ASPA overexpression with the knockdown of NAT8L led to a moderate phenotype between the two independent genetic modifications. Our findings of the metastasis-promoting effect of NAA depletion via ASPA overexpression leads to us believe that it is not just the accumulation of NAA but also its utilization that is important for breast cancer progression. Our future experiments are directed towards determining how NAA utilization causes a pro-tumorigenic phenotype. We would also like to study the current inconsistency between ASPA transcript levels in patient tumors and its observed tumor-promoting function in xenograft experiments. Completion of these studies will potentially define the importance of elevated NAA levels in the context of aggressive BCa. Since NAA is a metabolite that can be detected in serum, our study could also lead to the development of NAA as a non-invasive biomarker for early detection of aggressive BCa, thus providing a bigger window for therapeutic intervention. Citation Format: Akhila Balasubramanian, Weijie Zhang, Franklin Gu, Chandra Ambati, Nagireddy Putluri, Xiang Zhang, Aryan Namboodiri, Stefan Ambs, Arun Sreekumar. Role of the metabolite N-acetylaspartate in breast cancer progression [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-056.