Conclusion and Recomendation References

28 29 HPV types 16 and 18 increased the risk of cervical cancer 6 times than with out HPV infection. The study found that the risk of cervical cancer in HPV types 16 and 18 infections were 6 times in the case without HPV infection. The other studies reported that similar results but odds ratio was higher than this study as far as 43.5 for HPV type 16 and 24.8 for HPV type 18 [49,50]. In the abroad studies, the average odds ratio were 16-20 times for HPV oncogenic high risk group compared to that without HPV infection [34,49,51]. Therefore, the hypothesis that the risk of cervical cancer in case with HPV types 16 and 18 infections was higher than the case without HPV infection has been proven. The Risk of Expression of p53 in HPV Types 16 and 18 Infections Table 4. The Risk of Expression of p53 in HPV Types 16 and 18 Infections HPV types16 and 18 Odds Ratio Ci 95 p positive negative p53 positive 28 6 5,95 2,75-16,29 0,001 negative 29 37 HPV type 16 and 18 infection increased the risk of expression of p53 was 6 times than that with out HPV infection. The study found that the risk p53 expressions in HPV types 16 and 18 infections were 6 times and 3 times more than the case without HPV infection respectively. The abroad studies reported that the p53 increased in HPV type 16 infections were 14-26 times [50,52,53]. Some studies found that the high viral load and persistence correlated to the incidence of cervical cancer in situ [21,54]. Therefore, the risk of the detection of p53 expression in the case with HPV types 16 and 18 infections were higher than the case without HPV infection have been already proven. The Risk of Cervical Cancer in p53 positive Table 5.The Risk of Cervical Cancer in p53 and pRB positives Cervical cancer Odds Ratio Ci 95 p positive negative p53 positive 26 24 5,68 2,22-14,52 0,001 negative 8 42 P53 positive increased the risk of cervical cancer 6 times and 4,5 times respectively. This study found that the risk p53 positive increased the risk of cervical cancer were 6 times more than the case with p53 negative. The other studies reported that the p53 concentration was low in cervical cancer. It related to the natural degradation still worked [29,40], improperly metabolism of cancer cell [45,55], and the carcinogenesis may be ended [37,51]. Otherwise in precancerous lesions, the p53 was higher than in the invasive cervical cancer [49,51,54]. It can be understood that during process of the p53 wild type still exist and the oncoprotein E6 in precancerous or pre integration phase was not over expressed. Therefore, the risk of cervical cancer in the case with p53 expression higher than the case without p53 expression have been already proven. Based on the three proven results of this study, the carcinogenesis mechanism in HPV types 16 and 18 infections may be as below: The HPV infected the basal cell caused by α-6 integrin receptor for L1 HPV. The natural life cycle of HPV followed the cell differentiation. Protein E1 and E2 expressed early and stimulated immunity host response to a both early proteins. Meanwhile, the new viral forming was rolled by L2 continuing well undergo and immune host response to the L2 was not effective because of the completely virion was in exfoliate supericial cell. The cell was broken by E5 function and the trauma during sexual intercourse and the HPV become infectious. The natural life cycle was continuing forever and reinfected the basal cell. The E6 and E7 were expressed too but not as high as and it did not cause the function of p53 wild type to be impaired. Molecularly, instability of gene and immune response were performed. Histopathologically, the cervical lesion were the varieties of the dysplasia phases. When the viral load 50.000 and low expression of E1 and E2, to propose the integration between viral DNA to host DNA. And after integration, E6 and E7 oncoproteins over expressed and make E6-p53 and E7-pRB complexes. The complexes formation caused to the degraded of p53 and pRB functions. So the p53 can not control the damage gene, differentiation of cell, and apoptosis. The pRB-E7 complex caused E2F transcription factor freely and worked itself without any controlled of pRB. In addition, dysfunction of pRB inactivated c-myc and c-ras that kept the pathological coniguration of DNA. The E2F copied the pathologic gene or cervical cancer gen. Therefore the carcinogenesis of cervical cancer in HPV types 16 and 18 has been elucidated.

5. Conclusion and Recomendation

The total of 100 samples were divided into two groups consist of 50 cervical cancer as a cases and 50 non cervical cancer cases as a controls. The prevalence of HPV infection in cases and controls were 84.0 and 56.0 which consist of 78.0 and 36.0 HPV types 16 and 18. Meanwhile, the prevalence of p53 were 52.0 and 16.0, respectively. The study found : 1. The risk of cervical cancer in HPV types 16 and 18 infections was 6 times more than without HPV infection. 2. The risk of expressions of the p53 in HPV types 16 and 18 infections were 6 times more than without HPV infection. 3. The risk of cervical cancer for p53 positive were 5.5 times than p53 negative. Based on the result of this study, it is concluded that HPV types 16 and 18 infections are the major risk factors of cervical cancer and one of its carcinogenesis mechanism through the increasing of p53. Since the study was observational epidemiological analytic, it was needed a strong method to proof the cause effect of HPV types 16 and 18 infections in carcinogenesis of cervical cancer. Also recommended that a furthermore study could be conducted to know the correlation between p53 to clinical and histological indicators for better valid clinical conclusion.

6. References

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Up Date Terapi Kanker Serviks: Fokus Peran Radiologi Intervensi I Nyoman Bayu Mahendra 1 dan Ketut Suwiyoga 1 1 Fakultas Kedokteran Universitas Udayana Denpasar Bali Divisi Onko-Ginekologi Bagian Obstetri dan Ginekologi E-mail : bayu-mahendra-nyomanyahoo.com Abstrak Sampai saat ini di Indonesia selama 3 dasawarsa, kanker serviks masih menempati urutan pertama dimana umur semakin muda dan lebih 90 terdiagnosis pada stadium invasif, lanjut bahkan terminal. Hal ini merupakan area masalah yang serius dalam beberapa tahun mendatang; terkait dengan keberhasilan terapi. Keberhasilan terapi dengan modalitas operatif, kemoterapi, dan radioterapi konvensional baik sendiri-sendiri maupun kombinasi belum memuaskan terutama yang terkait dengan efektiitas dan toksisitasnya serta kualitas hidup. Selain itu, nutrisi ke tumor masih tetap berlangsung dan belum mendapat perhatian. Radiologi intervensi transarterial chemoteraphy TAC dan transarterial chemotherapy embolization TACE menjanjikan hasil yang lebih baik dibanding cara-cara konvensional tersebut dimana TACE lebih baik dibanding TAC dalam hal efektiitas, efek samping, dan kualitas hidup. Terkait dengan preservasi reproduksi maka metode ini diduga lebih menjanjikan. Efektivitas kemoterapi konvensional dan radiologi intervensi pada kanker serviks invasif secara keseluruhan masing-masing adalah 36,5 vs 41,4 CR,35,9 vs 52,9 PR, dan 10,3 vs 5,7 NR serta 45,2 vs 64,1 RR. Efek samping jangka pendek dan panjang berupa penekanan fungsi lever, ginjal, dan hemopoesis berbeda bermakna. Selain itu, timbulnya inkontinen fekal, diare, proktitis, dan sistitis serta gangguan pencernaan, kulit dan rambut berbeda bermakna. Dan, kualitas hidup masing-masing adalah 44,5 vs 64,5 DF, 21,4 vs 20,8 progresi, dan 15,9 vs 11,7 residif. Jadi, radiologi intervensi lebih menjanjikan dibanding operatif, kemoterapi dan kemoradiasi konvensional pada pengananan kanker serviks; terlebih pada kanker serviks invasif. Kata kunci: kanker serviks, radiologi intervensi

1. Pendahuluan