The effect of preventive human papillomavirus (HPV) vaccination on the reduction of the cervical cancer (CC) burden will not be known for 30 years. Therefore, it’s still necessary to improve the procedures for CC screening and treatment. The objective of this study was to identify and characterize cellular targets that could be considered potential markers for screening or therapeutic targets. A pyramidal strategy was used. Initially the expression of 8,638 genes was compared between 43 HPV16-positive CCs and 12 healthy cervical epitheliums using microarrays. A total of 997 genes were deregulated, and 21 genes that showed the greatest deregulation were validated using qRT-PCR. The 6 most upregulated genes (CCNB2, CDC20, PRC1, SYCP2, NUSAP1, CDKN3) belong to the mitosis pathway. They were further explored in 29 low-grade cervical intraepithelial neoplasias (CIN1) and 21 high-grade CIN (CIN2/3) to investigate whether they could differentiate CC and CIN2/3 (CIN2+) from CIN1 and controls. CCNB2, PRC1, and SYCP2 were mostly associated with CC and CDC20, NUSAP1, and CDKN3 were also associated with CIN2/3. The sensitivity and specificity of CDKN3 and NUSAP1 to detect CIN2+ was approximately 90%. The proteins encoded by all 6 genes were shown upregulated in CC by immunohistochemistry. The association of these markers with survival was investigated in 42 CC patients followed up for at least 42 months. Only CDKN3 was associated with poor survival and it was independent from clinical stage (HR = 5.9, 95%CI = 1.4–23.8, p = 0.01). CDKN3 and NUSAP1 may be potential targets for the development of screening methods. Nevertheless, further studies with larger samples are needed to define the optimal sensitivity and specificity. Inhibition of mitosis is a well-known strategy to combat cancers. Therefore, CDKN3 may be not only a screening and survival marker but a potential therapeutic target in CC. However, whether it’s indispensable for tumor growth remains to be demonstrated.
Objective: Recent reports suggest an increase in oral squamous cell carcinoma (OSCC) frequency. To improve programs in public health, it is necessary to understand the epidemiological conditions. The aim of this study was to analyze the trend in gender, age, anatomic zone and OSCC stage from Mexico City’s General Hospital patients from 1990 to 2008. Study design: A retrospective review of all OSCC cases diagnosed by the Pathology Department of the Mexico City General Hospital was performed. Demographic data, in addition to anatomic zone and histological degree of differentiation were obtained. Central tendency, dispersion and prevalence rate per 100,000 individuals were determined. Results: A total of 531 patients were diagnosed with OSCC; 58.4% were men, giving a male:female ratio of 1.4:1, and the mean age was 62.5 ± 14.9 years. The predominant anatomic zone was the tongue (44.7%), followed by the lips (21.2%) and gums (20.5%). The most frequent histological degree was moderately differentiated in 325 cases (61.2%). The rates of OSCC prevalence showed similar patterns in terms across time. A significant correlation (P = 0.007) between anatomic zone and age was observed. Conclusion: According to our results, the prevalence of OSCC does not show important variations; however, a relationship between age and anatomic zone was observed. These data could be used as parameters for the diagnosis of OSCC as well as for the development and dissemination of preventive programs for the early detection of oral cancer. Key words:Oral squamous cell carcinoma, prevalence, histology degree and anatomic zone.
Although human papillomavirus (HPV) infection is the main causal factor for cervical cancer (CC), there are data suggesting that genetic factors could modulate the risk for CC. Sibling studies suggest that maternally inherited factors could be involved in CC. To assess whether mitochondrial DNA (mtDNA) polymorphisms are associated to CC, HPV infection and HPV types, a case-control study was performed in the Mexican population. Polymorphism of mtDNA D-loop was investigated in 187 CC patients and 270 healthy controls. HPV was detected and typed in cervical scrapes. The expression of 29 mitochondrial genes was analyzed in a subset of 45 tumor biopsies using the expression microarray ST1.0. The Amerindian haplogroup B2 increased the risk for CC (odds ratio (OR)=1.6; 95% confidence interval (CI): 1.05-2.58) and enhanced 36% (OR=208; 95% CI: 25.2-1735.5) the risk conferred by the HPV alone (OR=152.9; 95% CI: 65.4-357.5). In cases, the distribution of HPV types was similar in all haplogroups but one (D1), in which is remarkable the absence of HPV18, a very low frequency of HPV16 and high frequencies of HPV45, HPV31 and other HPV types. Two mtDNA genes (mitochondrial aspartic acid tRNA (MT-TD), mitochondrial lysine tRNA (MT-TK)) could be involved in the increased risk conferred by the haplogroup B2, as they were upregulated exclusively in B2 tumors (P<0.01, t-test). Although the association of mtDNA with CC and HPV infection is clear, other studies with higher sample size will be needed to elucidate the role of mtDNA in cervical carcinogenesis.
This study aims to evaluate the clinicopathological features, TNM status, AJCC staging and behavior of squamous cell carcinoma of the tongue (SCCT) in patients older than 45 years. The files of the Department of Pathology of the Hospital General de México were reviewed and all cases of SCCT in patients older than 45 years were selected. Clinicopathological features, treatment, follow-up, microscopic diagnosis, and IJCC and TNM staging were retrieved. Complete data from 60 cases were evaluated. They were more common in males (mean age = 63.9 years). Unexpectedly a high rate of tumors (38.3%) were in the base of the tongue (BT). Moderately and poorly differentiated SCCT were the most common. 16.7% presented lymph node invasion, 15% were recurrent tumors and BT carcinomas recurred more frequently. A high rate (81.7%) were stage II and 48.3% were low-risk patients. SCCTs in the studied population displayed different clinico-pathological and behavioral features compared with worldwide data. Our results suggest that BT tumors should be treated more aggressively than those in the mobile tongue. BT located tumors were more frequent than previously published. Additional frequency studies will define outcomes in age cohorts with a consensus cutoff for young and elderly populations. More population-based studies should be performed in Latin American regions to acquire accurate data on SCC incidence in elder subpopulations and to identify precisely the etiological factors in these patients.
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