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  • ISSN: 2373-9436
    Volume 4, Issue 2
    Review Article
    Ghazi Alsbeih*, Medhat Elsebaie, Hadeel Almanea, Hatim Khoja, Asma Tulbah and Nasser Alrajhi
    Human Papillomavirus (HPV) is a DNA virus that infects the epithelial tissues without causing significant symptoms or signs and often cleared spontaneously by immunity. However, persistent infection and potential integration into host genome in a minority of infected patients could cause premalignant transformation that may progress to invasive cancer. The causative relationship between high-risk (HR) HPVs and cervical carcinoma is well established since the early seventies and had led to the development of the HPV vaccines. By far the HR HPVs 16 & 18 is the most common genotypes involved in cancer worldwide. Host genetic predisposition may play a pivotal role in the susceptibility to HPV-mediated transformation. The E6 and E7 viral oncoproteins of HR-HPVs associate with p53 and pRB proteins leading to loss of cell cycle control that predisposes to malignant transformation. Single nucleotide polymorphisms in TP53 and HDM2 were suggested to affect susceptibility to HPV.
    Emerging evidence involves HPV not only for anogenital cancers but also for a subset of Head and Neck and possibly colorectal and breast cancers. HPV-positive cancers appear to form separate subgroups among their counterparts with different epidemiology, histopathology, and response to chemo-radiation treatment. Over expression of p16 protein is being considered diagnostic for HPV and prognostic for treatment outcome. This was an important development in oncology to demonstrate that HPV-positive oropharyngeal cancers have p16-expression along with significantly improved outcomes, compared to HPV-negative patients. This has become the basis for "treatment deintensification" for HPV-positive cancers. The significance of HPV in colorectal and breast cancers is still to be clarified.
    Muhammad Kashif*, Nadeem Afzal, Muhammad ArslanTayyab, Faheem Shahzad and Shah Jahan
    Human papilloma viruses (HPVs) are involved not only in anogenital but also in head and neck carcinogenesis. So far almost 100 sub-types of HPV have been identified but HPVs 16, 18 and 31 are most common high risk types in oro-pharyngeal cancers. Since HPVs are involved in cancers, therefore, preventive and therapeutic options will reduce the prevalence, mortality and morbidity associated with HPV induced head and neck squamous cell carcinomas.
    Mesut Tez*
    Cancer has been accepted as a disease in which environmental or endogenous carcinogens induce mutations to oncogenes and tumor suppressor genes within a somatic cell [1]. However, various problems related to the mutation theory have been reported [2].
    Short Communication
    Helmy M. Guirgis*
    Background: California and Ohio are considering legislative measures to reduce prescription drug prices.
    Objectives: 1- Design a grading system to control costs and improve transparency of anticancer drugs. 2- Weigh costs and values in relative values (RV) in metastatic prostate cancer (mPC)
    Methods: Updated overall survival (OS), hazard ratios (HR) and dosage were utilized. Costs of 1-day of added OS were calculated. The 1-year-cost (yC) were graded (gr) A < 50,000, B $50,000 to $75,000, C > $7,500 to $100,000 and D > $100,000. The yC was divided by (1.0 –HR) and compared with cost/life-year gain (C/LYG). RV were computed as $50,000 or $100,000/C/LYG depending on lack vs. maintenance/improvement of quality of life (qol). Grade D was assigned to <0.20, C: 0.20 - <0.35, B: 0.35- 0.50 and A: > 0.50.
    Results: Costs, values and RV of generic docetaxel demonstrated A/gr. Cabazitaxel yC was $ 52,734 with B/gr and enzalutamide $108,348 with D/gr. In chemo-treated patients, RV of cabazitaxel was 0.19/D, abiraterone 0.39/B, enzalutamide 0.37/B and radium-223 0.39/B. In chemo-naïve, enzalutamide RV was 0.17/D. All drugs demonstrated wide differences between C/(1.0-HR) and C/LYG. The 2 values of radium-223 however were superimposed at the reported OS and HR.
    Conclusions: Docetaxel remains the most cost-effective drug in mPC management. The lowest values were demonstrated by enzalutamide in chemo-naive patients. Decisions based on costs without value consideration were misleading. Radium-223 demonstrated superimposed C/LYG and C/ (1.0- HR). The wide value discrepancy observed with other drugs suggests parallel use of survival and HR and warrants further investigation.
    Research Article
    Muniba Aban, Imran Siddqui, Muhammad Saboor, and Tariq Moatter*
    Introduction: In breast cancer, increased cyclooxygenase -2 expression is associated with poor prognosis. COX-2 expression influences production of pro-inflammatory prostaglandins. The present study investigated association between COX-2 promoter polymorphisms (rs689465, rs689466, rs20417) and histopathological features of breast cancer patients.
    Methods: We selected 150 HER-2 amplification positive breast cancer patients from our previous case-control study. The participants were evaluated for histopathological features and genotyped for COX-2 SNPs. Comparisons of genotype data with histopathological characteristics were performed by chi square test. Logistic regression was applied for estimation of odd ratios. COX-2 protein level and other markers were assessed by immunohistochemical staining. Statistical analyses were performed using SPSS version 19.0 and p value was set at <0.05.
    Results: Our data showed that elevated COX-2 expression was significantly associated with HER-2 amplified tumors (p=0.028). In addition, a positive association between rs20417 (GC+CC) and estrogen negative status (OR 2.7, 95%CI: 1.207-6.07, p = 0.016), HER-2 positive (OR 2.7, 95%CI: 1.138.-6.645, p = 0.02) and tumor type (OR 4.3, 95%CI: 1.148-16.263, p = 0.03) was noted. Eight haplotypes were deduced and associations with tumor size (p = 0.002), HER2 status (p =< 0.0001) and, ER status (p = 0.001) were observed. In addition, specific association showed that haplotype GAC was positively associated with Tumor size (OR 5.13, 95%CI: 1.140-23.13, p = 0.033) and HER-2 status (OR 2.018, 95%CI: 1.061-3.831, p = 0.032).
    Conclusion: Present study suggests that COX-2 expression and haplotypes of its associated SNPs should be considered for characterizing breast cancer prognosis.
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