Patricia Alonso de Ruiz

Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study

BACKGROUND Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. METHODS Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. FINDINGS 22,661 paraffin-embedded samples were obtained from 14,249 women. 10,575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6-50·4], 48·2 years [47·3-49·2], 46·8 years [46·6-48·1], and 55·5 years [54·9-56·1], respectively). INTERPRETATION To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45.

Cervical Cancer Screening in Developing Countries: Why Is It Ineffective? The Case of Mexico

BACKGROUND Mexico established a national cervical cancer-screening program in 1974. Despite the implementation of the program, there was a steady mortality trend of 16 per 100,000 women over 15 years. METHODS A diagnostic procedure of the pitfalls was applied to the following steps of the screening procedure: Pap sampling quality; cytological diagnosis validity; compliance of women; and determinants of non-participation. RESULTS The low effectiveness of screening on cervical cancer is principally due to factors associated with quality and coverage. Pap quality is deficient; 64% of a random sample of specimens lacked endocervical cells. Reading centers presented false negative indices of between 10 and 54%. Women seek screening in a late stage of disease (55% with cervical cancer seek care because they have symptoms). In addition, coverage is low; in women between 15 and 49 years of age in Mexico City, 64.2% have a history of Pap, compared with 30% in rural areas. Knowledge of what the Pap is used for strongly determines the use of screening. In rural areas, only 40% of women are informed about the purpose of the Pap test. CONCLUSIONS A proposal to reorganize Mexicos screening program includes the following five main strategies: (a) increased coverage; (b) improved quality control of how cervical smears are taken; (c) better interpretation of Pap tests; (d) guaranteed treatment for those whose tests show abnormalities, and (e) improved follow-up.

Factores que determinan la participación en el tamizaje de cáncer cervical en el estado de Morelos

Objective. To determine the main factors associated to participation in an early detection program of cancer (DPC), in a population with a high cervical cancer (CC) mortality rate. Material and methods. A population-based, crosssectional study was performed in the state of Morelos, which included 3 197 women aged between 15 and 49 years, randomly selected from a household sample frame of the 33 municipalities of the state. Results. Awareness of the utility of the Papanicolau (Pap) test (OR29.6, 95% CI 23.637) and a former history of gynecological symptoms (OR1.7, 95% CI 1.2-2.4) predisposed to greater use of the DPC. Factors associated to the use of the Pap test were precedents of using one contraceptive (OR1.4, 95% CI 1.1-1.8) or two or more contraceptives (OR2.1, 95% CI 1.6-2.8). Conclusions. In the sate of Morelos, Mexico, screening for cervical cancer is offered opportunistically in the context of health care use. Therefore, the precedent of using health care services is the main determining factor for use of the DPC program. These results reveal the need to design alternative strategies to promote participation among women who have no access to health services, since they

Potential impact of a 9-valent HPV vaccine in HPV-related cervical disease in 4 emerging countries (Brazil, Mexico, India and China)

BACKGROUND We estimated the potential impact of an investigational 9-valent human papillomavirus (HPV) vaccine (HPVs 6/11/16/18/31/33/45/52/58) in HPV-related cervical disease in Brazil, Mexico, India and China, to help to formulate recommendations on cervical cancer prevention and control. METHODS Estimations for invasive cervical cancer (ICC) were based on an international study including 1356 HPV-positive cases for the four countries altogether, and estimations for precancerous cervical lesions were extracted from a published meta-analysis including 6 025 HPV-positive women from the four mentioned countries. Globocan 2012 and 2012 World Population Prospects were used to estimate current and future projections of new ICC cases. RESULTS Combined proportions of the 9 HPV types in ICC were 88.6% (95%CI: 85.2-91.3) in Brazil, 85.7% (82.3-88.8) in Mexico, 92.2% (87.9-95.3) in India and 97.3% (93.9-99.1) in China. The additional HPV 31/33/45/52/58 proportions were 18.8% (15.3-22.7) in Brazil, 17.6% (14.2-21.2) in Mexico, 11.3% (7.5-16.1) in India and 11.9% (7.5-17.2) in China. HPV6 and 11 single types were not identified in any of the samples. Proportion of the individual 7 high risk HPV types included in the vaccine varied by cytological and histological grades of HPV-positive precancerous cervical lesions. HPV 16 was the dominant type in all lesions, with contributions in low grade lesions ranging from 16.6%(14.3-19.2) in Mexico to 39.8% (30.0-50.2) in India, and contributions in high grade lesions ranging from 43.8% (36.3-51.4) in Mexico to 64.1% (60.6-67.5) in Brazil. After HPV 16, variations in other majors HPV types were observed by country, with an under representation of HPV 18 and 45 compared to ICC. CONCLUSION The addition of HPVs 31/33/45/52/58 to HPV types included in current vaccines could increase the ICC preventable fraction in a range of 12 to 19% across the four countries, accounting the 9-types altogether 90% of ICC cases. Assuming the same degree of efficacy of current vaccines, the implementation of the 9-valent HPV vaccine in Brazil, Mexico, India and China would substantially impact on the reduction of the world cervical cancer burden.

Inter-observer variation in cytological and histological diagnoses of cervical neoplasia and its epidemiologic implication

Inter-observer variation in cytohistological diagnosis was assessed for 1506 cervical smears and 883 histological slides from four case-control studies on cervical neoplasia. The kappa statistic among a panel of three cytopathologists was highest for diagnosis of invasive cancer (0.70 for cytology and 0.74 for histology), followed by normal/inflammatory in cytology (0.68) and CIN III in histology (0.58). There was also nearly perfect agreement between the final panel diagnoses and the original diagnoses made by local cytopathologists, except for those of CIN III. Inter-observer variation in diagnosis for CIN III was inversely associated with age, number of children (in histology) and sexual activity (in cytology). However, the odds ratios for CIN III calculated by each cytopathologists diagnosis were not different from each other for any etiologic factor. These results indicate that the diagnoses of invasive cancer and of normal/inflammatory changes are highly reproducible and that the inter-observer variation does not have much impact on the etiologic risk estimates.

Cytologic criteria of cystic papillary carcinoma of the thyroid.

OBJECTIVE To establish differential cytologic criteria between benign and malignant thyroid cysts. STUDY DESIGN The study was a retrospective, transverse, analytic, comparative one of 3 groups of patients with nonfunctional thyroid nodules subjected to fine needle aspiration biopsy (FNAB) and surgical resection of the lesions, with histologic study as the diagnostic gold standard. Fifteen cases of cystic papillary carcinomas (group 1) with initial false negative diagnoses, 42 goiters accompanied by cystic degeneration (group 2) and 15 noncystic papillary carcinomas (group 3) were studied. Independent variables were age and sex; dependent variables were the presence of tridimensional fragments, papillae, anisonucleosis, nuclear bars, pseudoinclusions, powdery chromatin, cytoplasmic vacuoles, metaplastic cytoplasm, psammoma bodies, autolysis, multinucleated giant cells, spindle cells, colloid, monolayered laminae and macrophages in FNAB specimens. Statistical analysis was performed by central tendency measures and the chi 2 test. RESULTS The chi 2 test revealed a statistically significant difference between group 2 and the groups with papillary carcinoma based on the presence of tridimensional fragments, anisonucleosis, nuclear bars, pseudoinclusions, powdery chromatin, cytoplasmic vacuoles, metaplastic cytoplasm and autolysis. CONCLUSION The above cytologic characteristics must be searched for systematically in the FNAB of every cystic lesion of the thyroid to rule out the presence of cystic papillary thyroid carcinoma and to decrease the rate of false negative results.

El conocimiento de profesionales de la salud sobre la prevención del cáncer cervical. Alternativas de educación médica

Objective. Several studies have shown the importance of health care professionals as predictors of the use of cervical cancer screening (CCS). Material and methods. A cross- sectional study of 520 health care professionals in the State of Morelos during 1998, in order to evaluate and quantify their level of knowledge on the impact, etiology, screening, diagnosis and treatment of cervical cancer. A 1 to 10 scale questionnaire was given, and the sample included family medicine specialists, general practitioners, specialist and general nurses, and social workers. Statistical analysis included analysis of variance and 95% confidence intervals. Results. A knowledge mean of 4.74 (95% CI 4.57-4.88) was observed for a scale of 10; specialist physicians scored higher (mean 5.21, 95% CI 4.81-5.60) than social workers (mean 3.07, 95% CI 2.31-3.82). Periodicity of the Pap test in most cases was less than 1 year and there was poor consensus about the age period during which the Pap test should be obtained. The knowledge level was lower when trying to identify etiologic aspects and treatment perspectives. Conclusions. The results of this study show that, besides the improvement of undergraduate academic programs, it is necessary to improve educational interventions for health

CD3ζ Expression and T Cell Proliferation are Inhibited by TGF-β1 and IL-10 in Cervical Cancer Patients

IntroductionCervical cancer development from a squamous intraepithelial lesion is thought to be favored by an impaired T cell immunity. We evaluated parameters of T cell alterations such as proliferation, cytokine, and CD3ζ expression in peripheral blood and tumor-infiltrating T lymphocytes from women with squamous intraepithelial lesions (SIL) or cervical cancer (CC).Results and DiscussionT cell proliferation and cytokine messenger RNA (mRNA) expression were similar in women with SIL and healthy donors, whereas low T cell proliferation and lower mRNA expression of IL-2, IL-10 and IFN-γ were observed in women with CC. Moreover, infiltrating cells showed marginal responses. We also found that CD3ζ mRNA expression, whose protein is required for T cell activation, correlated with a decreased proliferation in advanced stages of the disease.ConclusionExperiments with T cells from healthy donors in the presence TGF-β1 or IL-10 suggest that these cytokines have a relevant role in T cell responses during CC progression.

The Positive Experience of Screening Quality Among Users of a Cervical Cancer Detection Center

BACKGROUND Our objective was to determine the main factors associated with increased utilization of a cervical cancer screening program (CCSP) in a population with a high mortality rate due to cervical cancer. METHODS A population-based study was carried out in the Mexican state of Morelos, Mexico. The study population included 3,197 women between the ages of 15 and 49 years who were selected at random using a State Household Sampling Framework in the State of Moreloss 33 municipalities. The sample included 2,094 women with a history of a previous Papanicolaou (Pap) test. RESULTS A previous experience of good screening quality is strongly associated with greater use of the CCSP (OR = 4.2; 95% confidence interval [CI], 1.6-10.9). The educational level of the head of the family is related to more frequent use of Pap smear services. Women whose husbands have 13 or more years of education (OR = 1.8; 95% CI 1.1-2.9) were more likely to have been screened. Similarly, women who had used two or more family planning methods (OR = 1.6; 95% CI 1.2-2.1) and those who knew why the Pap test was given (OR = 3.0; 95% CI 2.1-4.3) had a better history of Pap screening. CONCLUSIONS In areas where coverage of cervical cancer screening is low, a CCSP that guarantees the quality of all the different elements of care is essential if obstacles to cervical cancer prevention are to be eliminated. It is of particular importance to take into account and satisfy the perceptions and expectations of the women at risk.

Reproducibility study of cervical cytopathology in mexico: A need for regulation and professional accreditation

Due to the high rate of false negative results in diagnosis of cervical cytopathology, in many countries its practice has been transformed through the application of several interventions aimed at medical regulation to improve diagnostic accuracy.