DAFTAR ISI HALAMAN JUDUL
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DAFTAR ISI HALAMAN JUDUL ........................................................................................ i LEMBAR PENGESAHAN ............................................................................. ii PERNYATAAN PROMOVENDUS ............................................................... iii PRAKATA …………………………………………………………………... iv DAFTAR ISI .................................................................................................... ix DAFTAR TABEL ............................................................................................ xiv DAFTAR GAMBAR ....................................................................................... xvi DAFTAR LAMPIRAN .................................................................................... xix DAFTAR SINGKATAN ................................................................................. xx ABSTRAK ....................................................................................................... xxv BAB I PENDAHULUAN ................................................................................ 1 A. Latar Belakang ................................................................................ 1 B. Rumusan Masalah ............................................................................ 7 C. Tujuan Penelitian ............................................................................. 9 1. Tujuan umum ........................................................................... 9 2. Tujuan khusus .......................................................................... 9 D. Manfaat Penelitian ........................................................................... 9 1. Manfaat teoritis ........................................................................ 9 2. Manfaat praktis ......................................................................... 10 E. Keaslian Penelitian .......................................................................... x 10 BAB II TINJAUAN PUSTAKA ...................................................................... 13 A. Kanker Serviks ................................................................................ 13 1. Epidemiologi dan etiologi ........................................................ 13 2. Patogenesis dan perjalanan kanker serviks ............................... 16 3. Diagnosa kanker serviks ........................................................... 18 B. Human Papillomavirus (HPV) ........................................................ 22 1. Morfologi HPV ......................................................................... 22 2. Klasifikasi dan epidemiologi .................................................... 24 3. Patogenesis infeksi ................................................................... 26 4. Respon imun pada infeksi HR-HPV ......................................... 29 5. Perjalanan infeksi HPV menjadi kanker serviks ...................... 38 C. Toll-Like Receptor (TLR) ............................................................... 40 1. Jenis TLR dan ligan .................................................................. 40 2. Alur pensinyalan TLRs ............................................................. 45 3. Efek pensinyalan TLR .............................................................. 47 4. TLR dan infeksi Human Papillomavirus (HPV) ...................... 50 5. TLR dan inflamasi kronik ........................................................ 51 6. TLR dan sinyal menuju karsinogenesis .................................... 59 7. TLR dan kanker serviks ............................................................ 60 8. TLR dan terapi target ................................................................ 62 D. Kerangka Teori dan Kerangka Konsep ........................................... xi 66 1. Landasan teori/ kerangka teori .................................................. 66 2. Bagan kerangka teori ................................................................. 67 E. Kerangka Konsep ............................................................................ 68 F. Landasan Hipotesis .......................................................................... 68 BAB III METODE PENELITIAN .................................................................. 70 A. Desain Penelitian ............................................................................. 70 B. Tempat dan Waktu/ Jadwal Penelitian ............................................ 70 C. Sumber Data .................................................................................... 71 D. Populasi dan Sampel ........................................................................ 71 E. Kriteria Inklusi, Kriteria Eksklusi, dan Kriteria Drop Out .............. 72 F. Kerangka Sampel ............................................................................. 73 G. Tehnik Pengambilan Sampel ........................................................... 74 H. Cara Kerja ........................................................................................ 75 1. Identifikasi variabel .................................................................. 2. Definisi operasional .................................................................. 75 3. Pengumpulan data .................................................................... 76 4. Analisis data ............................................................................. 77 5. Penyajian data ........................................................................... 78 6. Interpretasi data ........................................................................ 78 7. Etika penelitian ......................................................................... 78 8. Bagan alur penelitian ................................................................ 79 xii 75 9. Prosedur pemeriksaan laboratorium ......................................... 80 a. Prosedur pemeriksaan HPV genotyping............................... 80 b. Prosedur pemeriksaan mRNA TLR7,8,9 ............................. 84 BAB IV HASIL PENELITIAN ....................................................................... 92 A. Karakteristik Subyek Penelitian ........................................................... 94 1. Berdasarkan umur …………………………………………… 94 2. Berdasarkan kelompok diagnosa ............................................. 95 3. Berdasarkan positivitas HPV ................................................... 96 B. Hasil Pemeriksaan mRNA TLR7 dan mRNA TLR9 ........................... 97 1. Optimalisasi metode pemeriksaan ekspresi mRNA TLR ........ 97 a. Desain primer ..................................................................... 97 b. Sintesa untai (strand) pertama cDNA ................................ 100 c. Pembuatan standar gen TLR7, TLR9 dan GAPDH ........... 101 2. Uji normalitas data mRNA TLR7 dan mRNA TLR9 .............. 103 3. Analisa berdasarkan diagnosis kanker dan pra kanker ……… 104 4. Analisa berdasarkan diagnosis Sq Ca, Adeno Ca, dan NIS 2/3 106 5. Analisa berdasarkan positivitas HPV ....................................... 108 a. Ekspresi mRNA TLR7 dan 9 berdasarkan positivitas HPV secara keseluruhan .................................................... 108 b. Analisa mRNA TLR7 dan 9 berdasarkan positivitas kelompok HPV 16 .............................................................. 110 xiii c. Analisa mRNA TLR7 dan 9 berdasarkan positivitas kelompok HPV 18 .............................................................. 111 d. Analisis mRNA TLR7 dan 9 berdasarkan positivitas kelompok HPV 16, 18, dan multi tipe ............................... 113 6. Berdasarkan kelompok tipe HPV pada Squamous carcinoma 115 C. Hasil Pemeriksaan HPV DNA Genotyping ......................................... 116 BAB V PEMBAHASAN ................................................................................. 130 A. Karateristik Subyek Penelitian ........................................................ 130 B. Pemeriksaan ekspresi mRNA TLR7 dan mRNA TLR9 .................. 132 C. Pemeriksaan HPV-DNA Genotyping ..................................... 144 D. Implikasi hasil penelitian ................................................................. 148 E. Keterbatasan penelitian .................................................................... 150 BAB VI KESIMPULAN DAN SARAN ......................................................... 152 A. Kesimpulan ...................................................................................... 152 B. Saran ................................................................................................ 154 DAFTAR PUSTAKA ...................................................................................... 156 RINGKASAN ……………………………………………………………….. 169 LAMPIRAN ..................................................................................................... 189 xiv