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    1. Copyright http://www.ilmukedokteran.net HPV dan kanker serviks Dr. Toto Imam Soeparmono, SpOG, K. Onk Subbag Ginekologi Onkologi Dep Obgin RSPAD Gatot Soebroto Jakarta Copyright http://www.ilmukedokteran.net
    2. Copyright http://www.ilmukedokteran.net Nama : Dr. Toto Imam Soeparmono, SpOG, K.Onk Pangkat : Letkol CKM / Nrp 31418 Jabatan : Kasub Instal Rawat Inap B Jabatan lain :1. Kadep obgin RSPAD 2. Ka Komite Penanggulangan Kanker terpadu RSPAD 3. Konsultan Kanker Kandungan Copyright http://www.ilmukedokteran.net
    3. Copyright http://www.ilmukedokteran.net  Umur : 48 thn  Status : K4  Dik Umum :1. Dokter umum (FK Unair 1987) 2. SpOG (FK Unsri 1997) 3. Konsultan Kanker Kan- dungan (FK UI 2005)  Dik Militer :1. PDAD (1987) 2. Selapa Kes (2006) Copyright http://www.ilmukedokteran.net
    4. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    5. Copyright http://www.ilmukedokteran.net Hmmmmmmmmm…………. TAPI, KENA KANKER SERVIKS Copyright http://www.ilmukedokteran.net
    6. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    7. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    8. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    9. Copyright http://www.ilmukedokteran.net Why?  Cervical cancer is a significant public health problem in many countries.  Cervical cancer is a sexually transmitted disease.  Cervical cancer is preventable (i.e., Methods of screening and treatment for precancerous lesions exist).  Pap Smear as a screening methods may not be appropriate or adequate for many low-resource settings. Copyright http://www.ilmukedokteran.net
    10. Copyright http://www.ilmukedokteran.net  Cervical cancer is one of the most common cancers, accounting for 6% of all malignancies in women. There are an estimated 16,000 new cases of invasive cancer of the cervix and 5,000 deaths in the U.S each year Copyright http://www.ilmukedokteran.net
    11. Copyright http://www.ilmukedokteran.net •Number 1 fatal cancer in women internationally. •More than 400,000 new diagnoses each year •More than 200,000 deaths (80% in developing countries)* *Reproductive Health Online, 2004. Available: http://www.rho.org Copyright http://www.ilmukedokteran.net
    12. Copyright http://www.ilmukedokteran.net  5th most common cancer in humans  2nd most common cancer in women  1st most common woman cancer in INA  Relatively early age of death  median of 57 years versus 72 years for other cancers  Great loss of productive years of life for each case Copyright http://www.ilmukedokteran.net
    13. Copyright http://www.ilmukedokteran.net Ranking of global female cancer incidence and mortality by site, 2002 Site Incidence Proportion (%) Mortality 1 Breast 1,151,298 410,712 0.36 2 Cervix uteri 493,243 273,505 0.55 3 Colon/rectum 472,687 250,532 0.53 4 Lung 386,891 330,786 0.85 5 Stomach 330,518 254,297 0.77 6 Ovary 204,499 124,860 0.61 7 Corpus uteri 198,783 50,327 0.25 8 Liver 184,043 181,439 0.98 Parkin DM, et al.Global Cancer Statistic, 2002 Copyright http://www.ilmukedokteran.net
    14. Copyright http://www.ilmukedokteran.net Ranking of cancer incidence by site in Indonesia, 1998 Site Number Proportion of total (%) 1 Cervix uteri 3686 17.85 2 Breast 2617 12.67 3 Skin 1270 6.15 4 Nasopharynx 1137 5,51 5 Rectum 1051 5.09 6 Ovary 1048 5.08 7 Lymphoma 926 4.48 8 Colon 653 3.16 Mangunkusumo R, 2005), Pidato Pengukuhan Copyright http://www.ilmukedokteran.net
    15. Copyright http://www.ilmukedokteran.net 1. Cervical Ca still a leading type of Ca among the woman 2. Ca Cervix represent 11 % of total cancer in woman and 66 % of gynecology Cancer 3. Overall survival rate cervical cancer in INA is low 4. Patients come to hosp. in the late stages 5. Death can prevent only by screening routinely 6. Adeno Ca of the cervix is increasing 7. Developing of the early detection and the management of the cervical cancer is important Copyright http://www.ilmukedokteran.net
    16. Copyright http://www.ilmukedokteran.net Normal Prakanker Kanker R S B Copyright http://www.ilmukedokteran.net
    17. Copyright http://www.ilmukedokteran.net Cervical Cancer NATURAL HYSTORY PRA -CANCER CANCER 15 % 30 % 45 % MILD MODERATE SEVERE NORMAL DYSPLASIA DYSPLASIA DYSPLASIA CANCER CANCER IN CITU INVASIVE 40 % 20 % Low Grade SIL High Grade SIL SCREENING Copyright http://www.ilmukedokteran.net
    18. Copyright http://www.ilmukedokteran.net  STAGE. 0 = PREINVASIVE CARCINOMA = CARCINOMA IN SITU Copyright http://www.ilmukedokteran.net
    19. Copyright http://www.ilmukedokteran.net  STAGE. I CONFINED TO UTERUS (EXTENSION TO CORPUS SHOULD BE DISREGARDED. STAGE. Ia. – DIAGNOSED ONLY BY MICROSCOPY STAGE. Ia.1 : - STROMAL INVASION </= 3 mm - HORIZONTAL SPREAD </= 7 mm STAGE. Ia.2 : - STROMAL INVASION >3 mm - </= 5 mm - HORIZONTAL SPREAD </= 7mm Copyright http://www.ilmukedokteran.net
    20. Copyright http://www.ilmukedokteran.net STAGE. Ib. CLINICALLY VISIBLE LESION CONFINED TO THE CERVIX OR MICROSCOPIC LESION GREATER THAN STAGE Ia.1. STAGE. Ib.1 : - GREATEST DIMENSION </= 4 cm. STAGE. Ib.2 : - GREATEST DIMENSION > 4 cm. Copyright http://www.ilmukedokteran.net
    21. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    22. Copyright http://www.ilmukedokteran.net  STAGE. II TUMOR INVADES BEYOND THE UTERUS BUT NOT TO PELVIC WALL OR TO LOWER THIRD OF THE VAGINA. STAGE. IIa. = WITHOUT PARAMETRIAL INVASION STAGE. IIb. = WITH PARAMETRIAL INVASION Copyright http://www.ilmukedokteran.net
    23. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    24. Copyright http://www.ilmukedokteran.net  STAGE. III TUMOR EXTENDS TO PELVIC WALL AND/OR INVOLVES LOWER THIRD OF THE VAGINA STAGE. IIIa. = INVOLVES LOWER THIRD OF VAGINA NO EXTENSION TO PELVIC WALL. STAGE. IIIb. = TUMOR EXTENDS TO PELVIC WALL AND/OR CAUSES HYDRONEPHROSIS OR NON- FUNCTIONING KIDNEY. Copyright http://www.ilmukedokteran.net
    25. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    26. Copyright http://www.ilmukedokteran.net  STAGE. IVa. . TUMOR INVADES MUCOSA OF BLADDER OR RECTUM AND/OR EXTENDS BEYOND TRUE PELVIS. STAGE. IVb. = DISTANT METASTASIS Copyright http://www.ilmukedokteran.net
    27. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    28. Copyright http://www.ilmukedokteran.net  HPV Infection  High number of sexual partners  Low social economic status  Smoking  History of STDs  Any combination of the above Copyright http://www.ilmukedokteran.net
    29. Copyright http://www.ilmukedokteran.net  Pada tahap prakanker sering tidak menimbulkan gejala sama sekali (92%)  kecuali ada infeksi: keputihan  Kalau sudah timbul gejala biasanya kanker sudah bertumbuh Copyright http://www.ilmukedokteran.net
    30. Copyright http://www.ilmukedokteran.net  Perdarahan pasca senggama  Keputihan  Gangguan lain akibat kanker sudah lanjut:  nyeri pinggul  gangguan BAB  gangguan BAK  BB menurun  lemah atau kurang darah akibat perdarahan Copyright http://www.ilmukedokteran.net
    31. Copyright http://www.ilmukedokteran.net  Treatment modalities based on stage  Side effects and toxicities of whole pelvic radiation and brachytherapy with chemotherapy  Sexual side effects of different treatment  Vaginal shortening  Vaginal coaptation with radiation therapy  Radiation necrosis  Loss of ovarian function  Decreased lubrication Copyright http://www.ilmukedokteran.net
    32. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    33. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    34. Copyright http://www.ilmukedokteran.net  Operasi  Radiasi  Khemoterapi  Kombinasi Copyright http://www.ilmukedokteran.net
    35. Copyright http://www.ilmukedokteran.net  Menganut terapi lesi pra kanker (Konisasi, LEEP, LETZ, Laser)  Untuk usia tua, jumlah anak cukup dilakukan sampel histerektomi (tipe I)  Follow up Copyright http://www.ilmukedokteran.net
    36. Copyright http://www.ilmukedokteran.net  Pada beberapa keadaan dapat dilakukan konisasi (Coppleson, 1992, Ostor, Roman)  Ekstra Facial Histerektomi  Follow up Copyright http://www.ilmukedokteran.net
    37. Copyright http://www.ilmukedokteran.net  Histerektomi Radikal, Diseksi KGB. (Tipe III)  Radiasi  Khemoterapi  Follow up Copyright http://www.ilmukedokteran.net
    38. Copyright http://www.ilmukedokteran.net Terapi Kanker Serviks Stadium IB 2 dan IIA, Tumor lebih 4 cm  Histerektomi Radikal + Diseksi KGB + Radioterapi ± Khemoterapi.  Terapi Radiasi pelvik + Khemoterapi.  Khemoradiasi sebagai Neo Ajuvan + Histerektomi Radikal Copyright http://www.ilmukedokteran.net
    39. Copyright http://www.ilmukedokteran.net  Primer radio terapi  Bisa ditambahkan khemoterapi  Perawatan Paliatif Copyright http://www.ilmukedokteran.net
    40. Copyright http://www.ilmukedokteran.net  Beberapa kasus kanker serviks stadium II B, dapat diberikan neo-ajuvan khemoradiasi atau khemoterapi, kemudian dilakukan histerektomi radikal.  Hal ini akan menambah 5 YSR. Copyright http://www.ilmukedokteran.net
    41. Copyright http://www.ilmukedokteran.net  Status dari kelenjar getah bening  Besar ukuran tumor primer  Kedalaman invasi stroma  Ada atau tidaknya invasi ke dalam pembuluh darah atau limfe  Jenis histopatologi dari sel kanker  Bebas atau tidaknya tepi vagina Copyright http://www.ilmukedokteran.net
    42. Copyright http://www.ilmukedokteran.net  Primer  Pre Operasi  Ajuvan  Paliatif Copyright http://www.ilmukedokteran.net
    43. Copyright http://www.ilmukedokteran.net  External Beam Radiotherapy (EBRT) Rotman, 1995, Morris, 1999)  Brachytherapy (BT)  Radioterapi Radikal (kombinasi EBRT dan BT) (Arrai, 1992) Copyright http://www.ilmukedokteran.net
    44. Copyright http://www.ilmukedokteran.net  Neo Ajuvan  Ajuvan  Kombinasi Kemoradiasi  Paliatif Copyright http://www.ilmukedokteran.net
    45. Copyright http://www.ilmukedokteran.net  P. V. B.  Paclitaxel + Carboplatin  Cisplatin + Hidroxyurea + 5 FU  Kombinasi – kombinasi yang lain Copyright http://www.ilmukedokteran.net
    46. Copyright http://www.ilmukedokteran.net  Intra operatif :  Perdarahan  Lesi pembuluh darah, ureter, buli – buli, rektum dan syaraf  Infeksi Copyright http://www.ilmukedokteran.net
    47. Copyright http://www.ilmukedokteran.net  Post Operatif Awal : Lanjut :  ISK  Gangguan Fungsi Buli2  Trombosis Vena  Lymphedema  Emboli Paru  Disfungsi seksual  Fistula  Demam  Limposis  Ileus  Obstruksi Ureter Copyright http://www.ilmukedokteran.net
    48. Copyright http://www.ilmukedokteran.net  Pada Kulit  Pada saluran cerna (mual, muntah, diare, rektal bleeding, proctitis karena radiasi)  Pada saluran kencing (hematuria) Copyright http://www.ilmukedokteran.net
    49. Copyright http://www.ilmukedokteran.net Komplikasi & Efek samping Khemoterapi 1. Sistim Hemopoetik : * Pansitopeni. 2. Sistim Gastrointestinal : * Mual muntah, diare. * Stomatitis. * Perdarahan saluran cerna. * Enterocolitis. 3. Immunosupressi. 4. Pada kulit : * Reaksi alergi, iritasi, sampai Steven Johnson Syndrome. * Alopecia. 5. Pada Hati : * Drug induced hepatitis. Copyright http://www.ilmukedokteran.net
    50. Copyright http://www.ilmukedokteran.net 6. Pada Paru-paru : * Interstitial pneumonitis. 7. Pada Jantung : * Kardiomiopati. 8. Pada Saluran Kencing : * Chronic azotemia * Acute renal failure * Retensi cairan. 9. Pada Sistim Saraf : * Neuropati. 10. Pada Pembuluh Darah : * Kerusakan pembuluh darah. Copyright http://www.ilmukedokteran.net
    51. Copyright http://www.ilmukedokteran.net 11. Terjadinya keganasan sekunder : * Leukemia 12. Pada Gonad : * Amenorrhoe. * Kegagalan fungsi ovarium. Infertilitas. 13. Gangguan Metabolik : * Hiponatremi * Hiperurisemi * Hipokalsemi. Copyright http://www.ilmukedokteran.net
    52. Copyright http://www.ilmukedokteran.net Tujuan :  Untuk mengetahui hasil yang segera dari pengobatan  Untuk mengidentifikasi komplikasi dari pengobatan  Untuk mendeteksi penyakit yang resisten atau rekuren Copyright http://www.ilmukedokteran.net
    53. Copyright http://www.ilmukedokteran.net Tahun I - II Setiap 3 bulan Tahun III – V Setiap 6 bulan Lebih dari 5 tahun Setiap tahun Copyright http://www.ilmukedokteran.net
    54. Copyright http://www.ilmukedokteran.net FIGO Stage % Cases 5-Year Survival I 46% 83% II 28% 64% III 21% 38% IV 4% 14% FIGO Annual Report. J Epi & Biostat 1998; 3(1) Copyright http://www.ilmukedokteran.net
    55. Copyright http://www.ilmukedokteran.net What is HPV? Copyright http://www.ilmukedokteran.net
    56. Copyright http://www.ilmukedokteran.net Cervical Cancer: History •1976- Meisels and Fortin noticed cervical neoplasias were saturated With small “koilocytes”… virus particles. Copyright http://www.ilmukedokteran.net
    57. Copyright http://www.ilmukedokteran.net  Double stranded virus, famili Papopa virus  Genome sirkuler 7- 8 kilo base-pairs (kbp) dibungkus kapsid berbentuk icosahedral  Untaian nukleotidenya : early region ( E1,2,4,5,6,7) late region ( L1,2) Copyright http://www.ilmukedokteran.net
    58. Copyright http://www.ilmukedokteran.net  Virion, Genome DNA:  double-stranded  circular  8000 base pair  Capsid:  a naked icosahedral  55 nm in diameter Copyright http://www.ilmukedokteran.net
    59. Copyright http://www.ilmukedokteran.net  Genome virus mempunyai 8 gen (ORFs = open reading frames): E (early)1, E2, E4, E5, E6, E7 serta L (late)1 dan L2  Absolutely tissue spesific  Target infeksi: basal keratinocytes  Ekspresi protein virus pada upper layer Copyright http://www.ilmukedokteran.net
    60. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    61. Copyright http://www.ilmukedokteran.net Regulation of Viral transcription & replication Growth E2 Stimulation E5 E4 Encodes for E1 minor capsid protein Regulation of viral L2 replication HPV genome (-7815 base pairs) Encodes for E7 major capsid Transforming genes/ protein growth stimulation L1 Late gene E6 URR ( Upper regulatory regions ) Gambaran Skematik dari organisasi genome HPV Copyright http://www.ilmukedokteran.net
    62. Copyright http://www.ilmukedokteran.net  HPV DNA :  > 99 % Ca Cx  94 % CIN  46 % normal Cytology Copyright http://www.ilmukedokteran.net
    63. Copyright http://www.ilmukedokteran.net  120 genotypes berbeda  tergantung sekuens DNA pada gen L1 yang meng- kode major capsid protein  30 tipe hidup pada mukosa anogenital  ada subtype dan varian  Terbagi menjadi:  cutaneous types  mucosotropic types Copyright http://www.ilmukedokteran.net
    64. Copyright http://www.ilmukedokteran.net Group Prototyp Site Acute Chronic e disease disease Cutan. 1,2 Skin Warts None Cutan-HR 5, 8 Skin Flat SCC lesions or Warts Mucos-LR 6, 11 Anogenital Warts None mucosa Mucos-HR 16, 18, Anogenital Flat SCC 31, 33, 45 mucosa, lesions oral mucosa Copyright http://www.ilmukedokteran.net
    65. Copyright http://www.ilmukedokteran.net Nonenveloped double- stranded DNA virus1  >120 types identified2  ~30–40 anogenital types2,3 ~15–20 oncogenic types*,2,3  HPV 16 and HPV 18 types account for the majority of worldwide cervical cancers.4 ~15-20 nononcogenic** types HPV 6 and 11 types are most often associated with external anogenital warts.3 *High risk; ** Low risk 1. Howley PM, Lowy DR. In: Knipe DM, Howley PM, eds. Philadelphia, Pa: Lippincott-Raven; 2001:2197–2229. 2. Schiffman M, Castle PE. Arch Pathol Lab Med. 2003;127:930–934. 3. Wiley DJ, Douglas J, Beutner K, et al. Clin Infect Dis. 2002;35(suppl 2):S210–S224. 4. Muñoz N, Bosch FX, Castellsagué X, et al. Int J Cancer. 2004;111:278–285. Copyright http://www.ilmukedokteran.net
    66. Copyright http://www.ilmukedokteran.net 14.6 HPV Type 16 18 69.7 45 25.7 31 North America/ Europe 17 33 52.5 52 67.6 58 South Asia 12.6 Others Northern Africa 57 Central/South Indonesia: 16 = 43,7 % America 18 = 39,4 % *A pooled analysis and multicenter case control study (N = 3607) 1. Muñoz N, Bosch FX, Castellsagué X, et al. Int J Cancer. 2004;111:278–285. Copyright http://www.ilmukedokteran.net
    67. Copyright http://www.ilmukedokteran.net Natural HPV Disease Progression Definitive Efficacy 0 to 1 Year 0 to 5 Years Up to 20 Years Persistent CIN Cervical Infection 2/3 Cancer Initial or HPV AIS Infx CIN 1 Cleared HPV Infection Copyright http://www.ilmukedokteran.net
    68. Copyright http://www.ilmukedokteran.net  High Risk types : 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82  Probable high risk types : 26, 53, and 66  Low risk type : 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108 (Munos et al, N Engl J Med 2003; 348:518-27) Copyright http://www.ilmukedokteran.net
    69. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    70. Copyright http://www.ilmukedokteran.net Routes of HPV Transmission Copyright http://www.ilmukedokteran.net
    71. Copyright http://www.ilmukedokteran.net Normal HPV Infection / CIN 2 / CIN 3 / Cervix CIN* 1 Cervical Cancer 1. Adapted from Goodman A, Wilbur DC. N Engl J Med. 2003;349:1555–1564. Copyright © 2003 Massachusetts Medical Society. All rights reserved. Adapted with permission. Copyright http://www.ilmukedokteran.net
    72. Copyright http://www.ilmukedokteran.net  Abstinence and lifetime mutual monogamy  risk avoidance Vs. risk reduction  Condoms offer little protection from infection but may reduce the likelihood of developing warts or cancer  Prophylactic vaccines offer strong promise for prevention in the future Copyright http://www.ilmukedokteran.net
    73. Copyright http://www.ilmukedokteran.net  Mucosotropic HPV virions tetap tinggal pd lokasi infeksi awal dan tidak memicu lisis sel  Dg terjadinya replikasi normal sel, antigenic capsid protein tdk diekspresikan sampai sel berdifferensiasi menjadi lapisan superfisial  Sel yg terinfeksi HPV resisten thd NK cells tapi dpt dilisis oleh cytokine-activated NK cells dan macrophage  perlu waktu untuk membersihkan infeksi dg sistem immune Copyright http://www.ilmukedokteran.net
    74. Copyright http://www.ilmukedokteran.net  Innate response terjadi segera, seroconversi menjadi antibodi thd HR-HPV bisa perlu waktu 6 bln sampai 1 tahun. Seroconversi untuk tipe LR hampir bersamaan dg saat infeksi  Antibodi thd protein capsid bisa bertahan sampai 10 – 15 tahun  Ab penting untuk mencegah infeksi dan re-infeksi  Strong cell-mediated response penting untuk viral clearance ( mell APC, T helper cells, cytolitic T cells dan costimulatory cytokines) Copyright http://www.ilmukedokteran.net
    75. Copyright http://www.ilmukedokteran.net  HPV sangat resistent terhadap panas dan proses pengeringan (desiccation).1  Transmisi non seksual melalui penggunaan alat-lat pribadi dapat juga terjadi, seperti penggunaan bersama handuk, pakaian yang telah terkontaminasi. 1  Kebanyakan infeksi HPV bisa bertahan selama 8 bulan dan kemudian menghilang. Namun sesudah 2 tahun, ditemukan sekitar 10% wanita masih membawa virus yang aktif dalam vagina dan serviks2 1.Roden RJ Infect Dis 1997;176:1076-9;2.McIntosh N JHPIEGO Str Papers 2000;8:1-14; Copyright http://www.ilmukedokteran.net
    76. Copyright http://www.ilmukedokteran.net HPV sulit dikultur Tes deteksi dan tipe HPV 3 tes : Hybrid Capture 2 ( HC2) Polymerase Chain Reaction (PCR) In Situ Hybridization (ISH) Copyright http://www.ilmukedokteran.net
    77. Copyright http://www.ilmukedokteran.net PENCEGAHAN DETEKSI DINI PENGOBATAN EDUKASI PAP SMEAR Kemoterapi Radioterapi KONDOM VIA Pembedahan VAKSINASI atau Konsultasi kepada dokter anda Copyright http://www.ilmukedokteran.net
    78. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    79. Copyright http://www.ilmukedokteran.net SANGAT PERLU Copyright http://www.ilmukedokteran.net
    80. Copyright http://www.ilmukedokteran.net  PREVENTIF ATAU  TERAPETIK Copyright http://www.ilmukedokteran.net
    81. Copyright http://www.ilmukedokteran.net Prophylactic vaccine Induction of effective humoral immune responses to protect from infection/antigen Therapeutic vaccine Stimulating cellular immune responses to eliminate the virally infected cell/antigen Bell MC, Alvarez RD.Int J Gynec Cancer, 2005,15: 4-12 Copyright http://www.ilmukedokteran.net
    82. Copyright http://www.ilmukedokteran.net  Cervarix® / GSK: - Vaksin Bivalen - Untuk HPV 16 dan 18 - Jadwal : 0 – 1 – 6  Gardasil® / MSD: - Vaksin Quadrivalen - Untuk HPV 16, 18 dan 6, 11 - Jadwal : 0 – 2 – 6  Suntik : im, deltoid Copyright http://www.ilmukedokteran.net
    83. Copyright http://www.ilmukedokteran.net Cancer cx is still a disease with high insidence mortality and costly Primary and secondary prevention can reduce incidence and cancer death Vaccine is an alternative in developing country that can not run and organized screening properly Copyright http://www.ilmukedokteran.net
    84. Copyright http://www.ilmukedokteran.net Hindari penyebab Hindari faktor resiko Deteksi dini VAKSINASI dg test Pap Jangan takut dengan perkataan KANKER Timbulkan keyakinan, bila ditemukan lebih dini, penyakit dapat disembuhkan Copyright http://www.ilmukedokteran.net
    85. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    86. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net
    87. Copyright http://www.ilmukedokteran.net Copyright http://www.ilmukedokteran.net

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