Cervicouterine Cancer Screening - TruScreen™ vs. Conventional Cytology: Pilot Study.

INTRODUCTION: Cervicouterine cancer (CC) is a health problem worldwide and is the fourth most common cancer in women, with a greater proportion of individuals affected by advanced stages of the disease in developing countries. OBJECTIVE: To determine the sensitivity and specificity of the TruScreen™ opto-electronic device vs. conventional cytology in CC screenings. METHODOLOGY: This is a prospective observational study that included individuals who presented for the first time at the Dysplasia Clinic of the Instituto Nacional de Cancerología from March 1 through April 30, 2016, and those referred due to abnormal conventional cytology. The patients were evaluated with the TruScreen™ device, conventional cytology, colposcopy and, if necessary, cervical biopsy. The results were analyzed by descriptive statistics as well as the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the TruScreen™, using conventional cytology as the standard. RESULTS: Thirty-two patients were included who met the inclusion criteria. The average age of the patients was 40 years (range, 23-61 years). For the diagnosis of high-grade intraepithelial lesions, the TruScreen™ device showed a 43% sensitivity, a 92% specificity, a PPV of 60%, and a NPV of 85%, whereas evaluation via cervical biopsy exhibited a 33% sensitivity, an 86% specificity, a 33% PPV, and an 86% NPV. The Kappa agreement index of the TruScreen™ with the colposcopies was 0.70. CONCLUSIONS: TruScreen™ demonstrated low sensitivity and high specificity compared with conventional cytology, which had a high NPV.

A phase II study of epigenetic therapy with hydralazine and magnesium valproate to overcome chemotherapy resistance in refractory solid tumors.

BACKGROUND: Epigenetic aberrations lead to chemotherapy resistance; hence, their reversal by inhibitors of DNA methylation and histone deacetylases may overcome it. PATIENTS AND METHODS: Phase II, single-arm study of hydralazine and magnesium valproate added to the same schedule of chemotherapy on which patients were progressing. Schedules comprised cisplatin, carboplatin, paclitaxel, vinorelbine, gemcitabine, pemetrexed, topotecan, doxorubicin, cyclophosphamide, and anastrozole. Patients received hydralazine at 182 mg for rapid, or 83 mg for slow, acetylators, and magnesium valproate at 40 mg/kg, beginning a week before chemotherapy. Response, toxicity, DNA methylation, histone deacetylase activity, plasma valproic acid, and hydralazine levels were evaluated. RESULTS: Seventeen patients were evaluable for toxicity and 15 for response. Primary sites included cervix (3), breast (3), lung (1), testis (1), and ovarian (7) carcinomas. A clinical benefit was observed in 12 (80%) patients: four PR, and eight SD. The most significant toxicity was hematologic. Reduction in global DNA methylation, histone deacetylase activity, and promoter demethylation were observed. CONCLUSIONS: The clinical benefit noted with the epigenetic agents hydralazine and valproate in this selected patient population progressing to chemotherapy' and re-challenged with the same chemotherapy schedule after initiating hydralazine and valproate' lends support to the epigenetic-driven tumor-cell chemoresistance hypothesis (ClinicalTrials.gov Identifier: NCT00404508).

Human papillomavirus-specific viral types are common in Mexican women affected by cervical lesions.

Cervical cancer (CC) is the most common in Mexican female population. The human papillomavirus (HPV) 16 and 18 frequencies in worldwide may be different due to geographical distribution. We analyzed the prevalence of HPV types and determinated their association in cervical lesion in a Mexican population. One hundred fifty-nine normal cervical smears, 95 low-grade squamous intraepithelial lesions (LGSIL), 59 high-grade squamous intraepithelial lesions (HGSIL), and 108 CC samples of the patients were collected. HPV types were determined by sequencing. We detected 11 high-risk types, four low-risk types, three not determinated, and two probably high risk. HPV were present in 12%, 57%, 88%, and 92% from normal, LGSIL, HGSIL, and CC samples, respectively. HPV 16 was the most common in all cervical lesions (71.6% in CC). HPV 58 was present in 18.6% of HGSIL, and the HPV 18 in 4.6% of CC. The 76% of all detected viruses belong to A9 species branch. Control women showed high percentage of HPV high-risk infection, suggesting that this is a high-risk group. High frequency of HPV 16 compared with a low incidence of HPV 18 was observed. HPV 58 is frequently detected in HGSIL but low frequency is found in CC. These findings might be considered for HPV screening.