Dulce María Hernández-Hernández

Association between high-risk human papillomavirus DNA load and precursor lesions of cervical cancer in Mexican women

OBJECTIVE Our objective was to determine the association between viral load of high risk human papilloma virus (HPV) using the Hybrid Capture II (HC II) system and cervical intraepithelial neoplasia (CIN) lesion stage. METHODS A total of 182 consecutive women with confirmed diagnoses of CIN 1-3 and 182 healthy women with negative Pap were included. All subjects underwent structured interviews focused on socioeconomic and reproductive factors. HC II testing was used to detect human papilloma virus (HPV) DNA. Viral load was measured by light measurements expressed as relative lights unit (RLU) ratio (specimens/control). Log(10)RLU ratios were categorized for analysis into four groups: negative (</=0); low viral load (0.01-1.0), middle viral load (1.01-2.0), and high viral load (2.0-3.6). Frequencies and association measurement odds ratio (OR) adjusted by unconditional multinomial regression (UMR) were used in analysis. RESULTS A total of 75 of 80 (93.7%) patients with CIN 2-3, 82 of 101 (79.4%) with CIN 1, and 36 of 182 (19.8%) controls were positive for HPV DNA. The higher the viral load of HPV DNA infection observed, the higher the probability of being associated with stage of CIN (P <0.001). Association between low viral load HPV and CIN 1 was 16.8 (7.2-39) compared with the highest association observed with high viral load and CIN 2-3 (OR(a) = 365.8, 94.7-1412). Both control and cases in the oldest women presented the highest viral load. CONCLUSIONS We found high frequencies of HPV DNA in CIN 1 and in CIN 2-3 patients. A clear association between viral load of HPV DNA was determined by HC II assay and CIN stage.

The role of macrophages and mast cells in lymphangiogenesis and angiogenesis in cervical carcinogenesis.

During carcinogenesis it is known that growth factors and cytokines from stromal and inflammatory cells from the microenvironment promote angiogenesis and lymphangiogenesis. However, the participation of macrophages and mast cells in these processes is not well understood. The aim of this study was to evaluate the relationship between mast cell and macrophage density with blood and lymphatic vessels in various stages of carcinoma of the uterine cervix. Tissue sections from archival paraffin-embedded samples from cases with cervical intraepithelial neoplasias (CIN) 1, 2, 3, carcinoma in situ, and invasive carcinoma were used. Immunohistochemical staining was done using the following antibodies: anti-LYVE-1; anti-CD31; anti-CD68, and anti-tryptase. Our results showed a significant increase in the number of macrophages in carcinoma in situ, a correlation between lymphatic vessels and macrophages in premalignant lesions CIN 2, and a correlation between mast cells and blood vessels in both CIN 2 and carcinoma in situ. In conclusion, our data underscore the importance of the recruitment of macrophages and mast cells in the development of tumor-associated blood and lymphatic capillaries.

Human leukocyte antigens I and II haplotypes associated with human papillomavirus 16-positive invasive cervical cancer in Mexican women.

Infection with human papillomavirus (HPV), mainly HPV type 16, is the major etiologic factor associated with cervical cancer (CC), but HPV infection alone is not sufficient for progression of precursor lesions. Host genetic susceptibility may lead to abnormal immune response resulting from virus persistence. Several studies have suggested a possible association with specific human leukocyte antigen (HLA) class I and II alleles and CC, but results are not consistent. The association of genetic HLA class I (A and B) and HLA class II (DR*B1 and DQ*B1) haplotypes with HPV16-positive CC (n = 104) and base population controls (n = 104) was evaluated in this Mexican population study. Sequence-specific primer HLA genes were determined by polymerase chain reaction (PCR)-based methods in peripheral blood cell counts (PCR sequence-specific oligonucleotides). The cervical swabs of 208 women were tested for HPV16 by Hybrid Capture II. Allele and haplotype HLA frequencies, Hardy-Weinberg tests, and a haplotype homogeneity test were estimated using the Arlequin software v. 3.01. Odds ratio (OR) was calculated to compare cases and control women. Consistent associations across other studies in women with CC and infected by HPV16 were observed for HLA-DRB1*15 (OR, 3.9; 95% CI, 1.6-10.2) and the haplotype DRB1*15 DQB1*0602 (OR, 4.1; 95% CI, 1.4-12.7) compared with control women. The HLA-A2-B44-DR4-DQ*0302, HLA-A24-B35-DR16-DQ*0301, and HLA-A2-B40-DR4-DQ*0302 haplotypes showed a positive association with CC (OR, >1), whereas HLA-A2-B39-DR4-DQ*0302, HLA-A24-B35-DR4-DQ*0302, and HLA-A68-B40-DR4-DQ*0302 showed a negative association (OR, <1). These results support the hypothesis that some HLA class I and II haplotypes could be involved with susceptibility for developing CC. Abbreviations: Cervical Cancer-CC, confidence interval-CI, human leukocyte antigens-HLA, human papillomavirus-HPV, odds ratio-OR, polymerase chain reaction-PCR, relative risk-RR, relative light units-RLU, ribonucleic acid-RNA, sequence-sensitive oligonucleotide-SSO

The hospital appropriateness evaluation protocol in elderly patients: a technique to evaluate admission and hospital stay

BACKGROUND Aging of the population represents one of the main challenges for health systems because of the increase in the demand for hospital services. To be able to count on tools that allow an objective evaluation of hospital-resource use becomes indispensable for health systems. OBJECTIVE To evaluate the reliability and validity of the Appropriateness Evaluation Protocol (AEP) regarding the appropriateness of admissions and hospital stays in elderly patients. In a scenario of scarce resources, to have a valid instrument will make it possible to evaluate the process of care in our growing elderly population in a standardized way. METHODS We carried out a retrospective study of 144 randomly chosen elderly patients admitted to the hospital with 394 even-numbered hospital-stay days. For the reliability analysis between the pair of nurses with the AEP and the pair of specialists, the details of the hospital admissions and the stay days were obtained from the clinical files. Criteria validity was conducted by pairs of physicians, including two internists, two general surgeons and two geriatricians. Only the agreements were compared with agreements of the AEP-trained nurses. Disagreements were excluded from the final analysis. RESULTS Inter-rater (inter-reviewer) agreement of hospital admissions and days spent by the patient presented a kappa coefficient of >0.70, while these admissions and hospital-stay days was >0.70. Sensitivity and positive predictor value to detect inappropriate admissions were not calculated because no agreement existed on inappropriate admissions. Specificity and negative predictive value to detect appropriate admission was >94.0% and >98.0%. Sensitivity and positive predictor value to detect inappropriate hospital-stay days was >44.0% and >10.0%, while specificity and negative predictor value for detecting appropriate hospital-stay days was >79.0% and >88.0%. CONCLUSIONS AEPs high-reliability and moderate-validity results with regard to clinical judgement positions it as a useful instrument for appropriate hospitalization screening in elderly patients.

Elective neck dissection in oral tongue cancer

IntroductionTreatment to the neck of patients with oral tongue cancer (OTC) without palpable nodes (cN0) is controversial. Elective neck dissection (END) could lead to over-treating more than 50% and follow-up indicates high regional recurrence. Decision to perform the surgery depends on the risk of hidden node metastases (NM).ObjectiveThe objective of this study was to assess the prevalence of hidden NM in cN0-OTC patients undergoing END.Material and methodsPatients (n=22) with cN0-OTC were treated with partial glosectomy and END.ResultsOf these, 16 were free of node metastases (negative predictive value=73%) while the other 6 (27%) showed at least one NM. Risk was greater, although statistically not significant, in T3 than in T1-2. Overall survival was better in patients without NM having END (95% versus 38%).ConclusionscN0-OTC is associated with 27% of NM, which justifies END. It is necessary to select carefully the candidates for END so as to preclude over-treatment in 73% of patients. Perhaps lymph mapping and sentinel node biopsy will help the better identification of hidden NM.ResumenIntroducciónEl tratamiento del cuello en pacientes con cáncer oral de la lengua (COL) sin ganglios palpables (cN0) es controvertido. La disección electiva de cuello (DEC) sobretrata al 50% de pacientes y la vigilancia implica alta recurrencia regional. La decisión del tratamiento depende del riesgo de metástasis ganglionares ocultas.ObjetivoEl objetivo es conocer la prevalencia de metástasis ganglionares ocultas en pacientes con COL sometidos a DEC.Material y métodosA 22 pacientes con COL, cN0 se les efectuó glosectomía y DEC.ResultadosUn total de 16 de 22 pacientes no tuvieron metástasis ganglionares (valor predictivo negativo=72,7%), mientras que 6 (27%) tuvieron metástasis ganglionares ocultas (MGO). El riesgo fue mayor en T3 que en T1-2 (diferencia no significativa). La supervivencia es mejor en pacientes sin MGO en la DEC(95% frente al 38%).ConclusionesEl COL se asocia al 27% de MGO, lo que justifica la DEC; se debe identificar a los candidatos a DEC para evitar sobretratar al 73%. El mapeo linfático y biopsia del ganglio centinela podría identificar pacientes con MGO.

ORIGINAL ARTICLE H-ras and Nm23-H1 Gene Expression and Proteolytic Activity in Squamous Cell Carcinoma of the Uterine Cervix

Background. The invasive and metastatic potential of malignant cells results from complex interactions of numerous factors not yet fully understood. Genomic alterations such as ras overexpression and nm23-H1 inhibition have been found to be frequently associated with increased invasiveness in various cancers. On the other hand, secretion of different proteinases are necessary for malignant cells to traverse a network of matrix macromolecules, but the relationship between the genomic alterations and the proteolytic phenotype is still unclear. Our aim was to investigate whether the appearance of the proteolytic phenotype had any correlation with the expression of H-ras and nm23-H1 genes in carcinoma of the uterine cervix. Methods. Twenty-five samples from patients with carcinoma of the uterine cervix at different clinical stages were studied. Cathepsin B1, plasminogen activator, and collagenase activity were assessed in tissue cytosols using specific synthetic oligopeptides as substrates. The expression of H-ras and nm23-H1 was investigated by means of immunohistochemistry and in situ hybridization. Results. Our results showed that cathepsin B1 was the most consistently elevated proteinase, demonstrating a linear correlation with clinical staging. H-ras expression was found elevated in 40% of the cases. Nm23-H1 protein immunoreactivity was positive in 40% of the cases. No correlation was found among H-ras, cathepsin B1 activity, and survival rate. Among cases with high cysteine proteinase activity, a different clinical behavior depending on the expression of Nm23-H1 was observed. The cases with Nm23-H1 protein had a markedly better survival rate than those lacking this protein. In contrast, the absence of Nm23-H1 in association with high cathepsin B1 activity was a clear indicator of a poor prognosis. Conclusions. These findings suggest a complex interaction between the proteolytic phenotype and the expression of H-ras and nm23-H1 genes in carcinoma of the cervix that influences the clinical behavior of the tumor.

An educational strategy for improving knowledge about breast and cervical cancer prevention among Mexican middle school students.

Introduction Prevention programs have not achieved the expected results in preventing mortality from breast and cervical cancer in Mexico. Therefore, we propose a complementary strategy. Methodology An educational strategy for high school students in Mexico (2011–2013) was designed (longitudinal design, two measurements and a single intervention). The postintervention assessment included: 1) knowledge acquired by students about cancer prevention and 2) The performance of the student as a health promoter in their household. The strategy was based on analysis of cases and developed in three sessions. An assessment tool was designed and validated (Test–Retest). The levels of knowledge according to the qualifications expected by chance were determined. Wilcoxon test compared results before and after intervention. Results An assessment instrument with 0.80 reliability was obtained. 831 high school students were analyzed. Wilcoxon rank-sum test showed a significant learning after the intervention (Z = − 2.64, p = 0.008) with improvement of levels of knowledge in a 154.5%. 49% of students had a good performance as health promoters. Conclusions The learning in preventive measures is important to sensitize individuals to prevention campaigns against cancer. This strategy proved to improve the level of knowledge of students in an easy and affordable way.

Prevalence of human Papillomavirus in head and neck cancer in Mexico: a case-control study

Address: 1Facultad de Quimica, UNAM, Ciudad Universitaria, Mexico City, Mexico, 2Division of Research, Instituto Nacional de Cancerologia (INCan), Mexico City, Mexico, 3Medical Research Unit in Oncology Diseases, Pathology Department, Oncology Hospital, Centro Medico Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico and 4Instituto de Investigaciones Biomedicas, UNAM, Ciudad Universitaria, Mexico City, Mexico