THE RELATIONSHIP OF PARITY TO THE HISTOPATHOLOGICAL TYPES OF UTERINE CERVICAL CARCINOMA AT DR.

SARDJITO GENERAL HOSPITAL OF YOGYAKARTA

SUMMARY

To Fulfill a Partial Requirement To Obtain a Masters Degree Maternal and Child Health Reproductive Health Study Program of Public Health Sciences

ANYTA RAHMAWATI NIM: 07/260984/PKU/09285

POST GRADUATE PROGRAM FACULTY OF MEDICINE UNIVERSITAS GADJAH MADA YOGYAKARTA 2012

APPROVAL SHEET

SUMMARY

THE RELATIONSHIP OF PARITY TO THE HISTOPATHOLOGICAL TYPES OF UTERINE CERVICAL CARCINOMA AT DR. SARDJITO GENERAL HOSPITAL OF YOGYAKARTA

Submitted by:

ANYTA RAHMAWATI NIM: 07/260984/PKU/09285

Approved by:

Main Advisor

Prof. dr. Djaswadi Dasuki, SpOG., MPH.,PhD.

Approval date.

Co Advisor

dr. H. Heru Pradjatmo, M.Kes, SpOG(K)

Approval date....

CHAPTER I BACKGROUND

Cervical cancer is one of the neoplastic disease most often affecting women in the world. About 85% incidence of cervical cancer occur in developing countries.(1,2,3) One of the prognostic factors of cervical cancer is a type of histopathology. The histopathologic type most affecting women is cervical squamous cell carcinoma, while the type of adenocarcinoma tends to be fewer, but the incidence continues to rise in recent years.(4,5,6) Cervical adenocarcinoma has a cause, epidemiology and biological different from squamous cell carcinoma and one of the distinguishing factors is parity.(4,7) High parity is known as a risk factor for cervical cancer.(3) However, a study found strong evidence that there is a relationship between nulliparous and cervical adenocarcinoma.(4) Based on the description above, the formulation of the problem in this study was "whether nulliparous effects on the incidence of cervical adenocarcinoma?" CHAPTER II LITERATURE REVIEW

1. Cervical carcinoma Cervical carcinoma is the relentless growth of abnormal tissue in the cervix uteri. The cervix is located at the lower end of the uterus that protrudes into the vagina.(8) There are two main types of cervical cancer, namely: (9) a. Squamous cell carcinoma This type of cancer develops from cells lining the inside of the cervix, called squamous cells. An increased risk of squamous cell carcinoma is associated with an increased number of regular sexual partners, too

young age at the time to have sex, use of oral contraceptives, high parity, early age at first birth and smoking in a long time.(4,5) b. Adenocarcinoma Adenocarcinoma arises from one of the columnar epithelia in the gastrointestinal endocervix or from the tubular gland.(10) A study mentioned that there are a significant number of nulliparous diabetes women among patients with cervical adenocarcinoma compared to squamous cell carcinoma group. Potential risk factors for increasing prevalence of cervical adenocarcinoma is nulliparity and obesity.(5) 2. Parity High parity is one of the factors that may increase the risk of cervical cancer.(3) Women with high parity and too young age at the time of first birth are two risk factors for squamous cell carcinoma. A study found a strong correlation between nulliparity and cervical adenocarcinoma.(5) CHAPTER III METHODS

This was an observational analytic study with a case-control design through a quantitative approach. The data used were secondary data from medical records of cervical cancer patients enrolled from January 1, 2007 through December 31, 2008. The control group was patients of cervical squamous cell carcinoma and the case group was patients with cervical adenocarcinoma; each group consisted of 87 patients. The dependent variable was the type of cervical carcinoma histopathology. The independent variable was parity. The extraneous variables were patient's age, education level, age of first marriage, age of menarche and body mass index (BMI). Data analysis was performed by the method of statistical analysis using STATA software version-11 program, including univariable analysis, bivariable analysis and multivariable analysis.

CHAPTER IV RESULTS AND DISCUSSION

Picture of the characteristics of research subjects based on the independent variable showed that 7.5% of the subjects were nulliparous women. Subjects tended to have lower education levels (58.1%). The majority of research subjects first marriage was at age more than 16 years as many as 86.7%. Menstrual status of study subjects showed that most age group at menarche was less than 13 years, amounting to 61.5%. A total of 50.6% subjects had normal body mass index. Based on the ROC curves, the cutoff point in the parity variable was 4. The results of this study showed a significant relationship between parity and histopathological types of cervical cancer as evidenced by the value of OR = 2.48 (95% CI = 1.06 to 6.07). This means that the chances of finding women with parity 0-4 in cervical adenocarcinoma group were 2.48 times higher than those in the cervical squamous cell carcinoma group. Women with parity 0-4 were more common found in cervical adenocarcinoma group, whereas women with parity more than 5 were more common in squamous cell carcinoma group. High parity increases the risk of cervical carcinoma because it causes the transformation zone in eksoserviks for several years and this makes it is easier for the direct exposure of HPV and other cofactors. (4) The mean of the younger age was found in patients with adenocarcinoma. The study conducted in 1976-2000 on the incidence of cervical adenocarcinoma and carcinoma in the United States suggested that the average invasive adenocarcinoma was seen to rise, especially in young women.
(11)

The majority of patients with cervical cancer were

poorly educated. Perhaps this could be attributed to low socio-economic factors as well that would eventually result in marriage in a young age. These factors made them more easily ill and not able to avoid diseases that was actually avoidable, such as cervical cancer.

Age of first marriage with histopathological types of cervical carcinoma was found no significant relationship. This result was consistent with a research conducted in 2003 which stated that the age of first intercourse was not associated with cervical adenocarcinoma, but associated with cervical squamous cell carcinoma. The analysis results of the menstruation variable obtained information that the age of menarche was associated with cervical adenocarcinoma. This result was in contrast with a study on the role of parity and HPV virus in cervical carcinoma which showed that at the age of menarche was not a risk to both types of cervical cancer (cervical adenocarcinoma and squamous cell carcinoma). (3) The result of multivariable analysis with linear regression analysis showed that parity remained consistent influencing the histopathologic type after being controlled with menarche age, although the effect finally became small. CHAPTER V CONCLUSIONS AND RECOMMENDATIONS

The conclusions in this study are that parity affected the histopathological types of cervical carcinoma. The cutoff point of parity was 4 children. Women with parity 0-4 were 2.48 times more common in the group of patients with cervical adenocarcinoma whereas women with parity more than 5 were found in patients with cervical squamous cell carcinoma. Based on the conclusions, the suggestion that can be proposed is the need to increase coverage of screening / early detection of cervical carcinoma in both women with high risk and low risk.

REFERENCES 1. Nojomi M, Modaresgilani M, Mozafari N, Erfany A. Cervical cancer and duration of using hormonal contraceptives. Asia-Pac J Clin Oncol. 2008; 4: 107-112. 2. Wittet S, Tsu, V. Cervical cancer and the millennium development goals. Bull World Health Organ. 2008; 86 (6): 488-491 3. Munoz N, Bosch X, Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders P, Meijer CJLM. Epidemiologic classification of human pappilomavirus types associated with cervical cancer. N Engl J Med, 2003; 348: 518-27. 4. Altekruse SF, Lacey JVJ, Brinton LA, Gravitt PE, Silverberg S, Barnes, WAJ, Greenberg MD, Hadjimichael OC, McGowan L, Mortel R, Schwartz PE, Hildesheim A. Comparison of human papillomavirus genotypes, sexual, and reproductive risk factors of cervical adenocarcinoma and squamous cell carcinoma: Northeastern United States. Am J Obstet Gynecol, 2003; 188: 657663. 5. Green J, Gonzales AB, Sweetland S, Beral V, Chilvers C, Crossley B, Deacon J, Hermon C, Pha J, Mant D, Peto J, Pike M, Vessey MP Risk factors for adenocarcinoma and squamous cell carcinoma of the cervix in women aged 2044 years: the UK National Case Control Study of Cervical Cancer . British Journal of Cancer. 2003; 89: 2078 2086. 6. Vizcaino AP, Moreno V, Bosch FX, Munoz N, Barros-Dios XM, Parkin, DM. International trends in the incidence of cervical cancer: I. Adenocarcinoma and adenosquamous cell carcinomas. Int J Cancer. 1998; 75: 536545. 7. Brinton LA, Tashima KT, Lehman, HF, Levine RS, Mailin K, Savitz, DA, Stolley PD, Fraumeni JF. Epidemiology of cervical cancer by cell type. Cancer Res. 1987; 47: 1706-1711. 8. Moechherdiyantiningsih. Epidemiologi dan pengendalian kanker serviks. Medika. 2000 26; 3: 166-171. 9. American Cancer Society. 2008. Detailed guide: cervical cancer, what is cervical cancer?. Available from: <http://www.cancer.org/docroot/CDG/cdg_0.asp> [Accessed 24 November 2008] 10. Parsons L. & Sommers SC. Gynecology. Philadelphia:W.B Saunders Company. 1964 11. Wang SS, Sherman ME, Hildesheim A, Lacey JV & Devesa S. Cervical adenocarcinoma and squamous cell carcinoma incidence trends among white women and black women in the United States for 1976-2000. American Cancer Society. 2004;100:1035-1044.

HUBUNGAN PARITAS DENGAN JENIS HISTOPATOLOGI KARSINOMA SERVIKS UTERI DI RSUP Dr. SARDJITO YOGYAKARTA

RINGKASAN

Untuk Memenuhi Sebagian Persyaratan Mencapai Derajat Sarjana S-2

Minat Kesehatan Ibu dan AnakKesehatan Reproduksi Program Studi Ilmu Kesehatan Masyarakat

Diajukan oleh: ANYTA RAHMAWATI NIM: 07/260984/PKU/09285

Kepada

PROGRAM PASCASARJANA FAKULTAS KEDOKTERAN UNIVERSITAS GADJAH MADA YOGYAKARTA 2012

Lembar Persetujuan

HUBUNGAN PARITAS DENGAN JENIS HISTOPATOLOGI KARSINOMA SERVIKS DI RSUP Dr. SARDJITO YOGYAKARTA

RINGKASAN Diajukan Oleh:

ANYTA RAHMAWATI NIM: 07/260984/PKU/09285

Telah disetujui oleh:

Pembimbing Utama

Prof. Djaswadi Dasuki, SpOG (K). MPH, Ph.D,

Tanggal: ............................

Pembimbing Pendamping

dr. H. Heru Pradjatmo, M.Kes, SpOG(K)

Tanggal: ............................

16

BAB I LATAR BELAKANG

Kanker serviks merupakan salah satu penyakit neoplastik yang paling sering diderita wanita di dunia. Sekitar 85% kejadian kanker serviks terjadi di negara berkembang.(1,2,3) Salah satu faktor prognosis dari kanker serviks adalah jenis histopatologi. Jenis histopatologi yang paling banyak diderita wanita adalah karsinoma sel skuamosa servik, sedangkan adenokarsinoma lebih sedikit, tetapi insidennya terus meningkat pada beberapa tahun terakhir.(4,5,6) Adenokarsinoma serviks mempunyai penyebab, epidemiologi dan biologis yang berbeda dari karsinoma sel skuamosa, salah satu pembedanya adalah paritas.(4,7) Paritas tinggi diketahui sebagai faktor risiko kanker serviks.(3) Tetapi studi penelitian menemukan bukti kuat bahwa ada hubungan antara nulipara dengan adenokarsinoma serviks.(4) Berdasarkan uraian latar belakang diatas, maka rumusan masalah dalam penelitian ini adalah apakah nulipara berpengaruh terhadap kejadian adenokarsinoma serviks? BAB II TINJAUAN PUSTAKA 1. Karsinoma serviks Karsinoma serviks adalah pertumbuhan tanpa henti jaringan abnormal di dalam serviks uteri. Serviks terletak di bagian ujung bawah uterus yang menonjol ke vagina.(8) Terdapat dua jenis utama dari kanker serviks, yaitu:(9) a. Karsinoma sel skuamosa Kanker jenis ini berkembang dari sel yang melapisi bagian dalam dari serviks, yang disebut sel skuamosa.. Peningkatan risiko karsinoma sel skuamosa berhubungan dengan peningkatan jumlah pasangan seksual regular, usia yang terlalu dini pada saat melakukan hubungan

27

seksual, penggunaan kontrasepsi oral, paritas tinggi, usia dini pada saat melahirkan pertama kali dan merokok dalam waktu yang lama.(4,5) b. Adenokarsinoma Adenokarsinoma muncul dari salah satu lapisan epitel kolumner pada saluran endoserviks atau dari glandula tubulus. pada wanita diabetes serviks dan nullipara diantara kelompok pasien
(10)

Studi

penelitian menyebutkan bahwa terdapat jumlah besar yang signifikan dengan sel adenokarsinoma dibandingkan karsinoma

skuamosa. Faktor risiko yang berpotensi untuk meningkatkan prevalensi adenokarsinoma serviks adalah nuliparitas dan obesitas.(5) 2. Paritas Paritas tinggi merupakan salah satu faktor yang dapat meningkatkan risiko terjadinya kanker serviks.(3) Wanita dengan paritas tinggi dan usia yang terlalu muda pada saat melahirkan pertama kali merupakan faktor risiko teradinya karsinoma sel skuamosa. Studi penelitian menemukan adanya hubungan yang kuat antara nuliparitas dengan adenokarsinoma serviks.(5) BAB III METODE PENELITIAN Jenis penelitian observasional analitik dengan rancangan kasuskontrol melalui pendekatan kuantitatif. Data yang digunakan adalah data sekunder berupa rekam medis pasien kanker serviks yang terdaftar dari tanggal 1 Januari 2007 sampai dengan 31 Desember 2008. Kelompok kontrol adalah pasien karsinoma sel skuamosa serviks dan kelompok kasus adalah adenokarsinoma serviks, setiap kelompok terdiri dari 87 pasien. Sebagai variabel terikat adalah jenis histopatologi karsinoma serviks. Variabel bebas adalah paritas. Variabel luar adalah umur pasien, tingkat pendidikan, umur pertama kali menikah, umur menarche dan Indeks Massa Tubuh (IMT). Analisis data dilakukan dengan metode analisis statistik menggunakan software program STATA versi-11, meliputi analisis univariabel, analisis bivariabel dan analisis multivariabel.

8 3

BAB IV HASIL PENELITIAN DAN PEMBAHASAN

Gambaran karakteristik subjek penelitian berdasarkan variabel independent menunjukkan bahwa 7,5% dari subjek penelitian adalah wanita nulpara. Subjek penelitian cenderung memiliki tingkat pendidikan rendah (58,1%). Mayoritas subjek penelitian pertama kali menikah pada umur >16 tahun yaitu sebanyak 86,7%. Status menstruasi subjek penelitian menunjukkan bahwa umur menarche paling banyak pada umur < 13 tahun, yaitu 61,5%. Sebanyak 50,6% subjek penelitian memiliki Indeks Massa Tubuh normal. Berdasarkan hasil ROC curves, nilai ambang batas pada variabel paritas adalah 4. Hasil penelitian ini menunjukkan adanya hubungan bermakna antara paritas dengan jenis histopatologi kanker serviks yang dibuktikan dengan nilai OR=2,48 (95%CI=1,06-6,07). Artinya kemungkinan menemukan wanita dengan paritas 0-4 pada kelompok adenokarsinoma serviks lebih tinggi 2,48 kali dibandingkan pada kelompok karsinoma sel skuamosa serviks. Wanita dengan jumlah paritas 0-4 lebih banyak ditemukan pada kelompok adenokarsinoma serviks, sedangkan wanita dengan paritas >5 lebih banyak ditemukan pada kelompok karsinoma sel skuamosa. Paritas tinggi meningkatkan risiko karsinoma serviks karena menyebabkan zona transformasi berada di eksoserviks untuk beberapa tahun, hal ini yang mempermudah paparan langsung dari HPV dan kofaktor yang lain.(4) Nilai mean umur yang lebih muda ditemukan pada penderita jenis adenokarsinoma. Penelitian yang dilakukan pada 1976-2000 tentang insiden adenokarsinoma dan karsinoma serviks di Amerika Serikat menyebutkan bahwa rata-rata invasif adenokarsinoma terlihat meningkat, terutama pada wanita muda.
(11)

Sebagian besar penderita kanker leher

rahim adalah berpendidikan rendah. wanita yang memiliki pendidikan rendah kurang respon terhadap skrining kanker leher rahim di India.

9 4

Pendidikan memiliki hubungan dengan pengetahuan akan skrining kanker leher rahim. Mungkin hal ini dapat dihubungkan dengan faktor sosial ekonomi yang rendah pula yang pada akhirnya akan mengakibatkan terjadinya perkawinan umur muda. Faktor-faktor ini membuat mereka lebih mudah sakit dan tidak dapat menghindari penyakit-penyakit yang bisa dicegah, misalnya kanker serviks. Umur pertama kali menikah dengan jenis histopatologi karsinoma serviks tidak didapatkan hubungan yang signifikan. Hasil ini sejalan dengan penelitian yang dilakukan pada tahun 2003 yang menyebutkan bahwa umur pertama kali intercourse tidak berhubungan dengan adenokarsinoma serviks, tetapi berhubungan dengan karsinoma sel skuamosa serviks. Hasil analisis variabel menstruasi, diperoleh informasi bahwa umur menarche berhubungan dengan adenokarsinoma serviks. Hasil ini berlawanan dengan penelitian tentang peran paritas dan virus HPV pada karsinoma serviks yang menunjukkan bahwa pada umur menarche tidak berisiko pada kedua jenis kanker serviks (adenokarsinoma serviks dan karsinoma sel skuamosa). (3) Hasil analisis multivariabel paritas dengan analisis regresi linier menunjukkan bahwa tetap konsisten mempengaruhi jenis

histopatologi setelah dikontrol dengan umur menarche, walaupun pengaruhnya menjadi kecil setelah dikontrol dengan umur menarche. BAB V KESIMPULAN DAN SARAN Kesimpulan dalam penelitian ini adalah nuliparitas tidak berpengaruh terhadap kejadian adenokarsinoma serviks. Nilai ambang batas dari paritas yang dapat mempengaruhi kejadian adenokarsinoma serviks adalah 4 anak. Wanita dengan paritas 0-4, 2,48 kali ditemukan lebih banyak pada kelompok penderita adenokarsinoma serviks, sedangkan wanita dengan paritas >5 banyak ditemukan pada penderita karsinoma sel

10 5

skuamosa

serviks.

Saran

dalam

penelitian

ini

adalah

perlunya

peningkatan cakupan skrining/deteksi dini karsinoma serviks baik pada wanita dengan risiko tinggi maupun rendah.

KEPUSTAKAAN 1. Nojomi M, Modaresgilani M, Mozafari N, Erfany A. Cervical cancer and duration of using hormonal contraceptives. Asia-Pac J Clin Oncol. 2008; 4: 107-112. 2. Wittet S, Tsu, V. Cervical cancer and the millennium development goals. Bull World Health Organ. 2008; 86 (6): 488-491 3. Munoz N, Bosch X, Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders P, Meijer CJLM. Epidemiologic classification of human pappilomavirus types associated with cervical cancer. N Engl J Med, 2003; 348: 518-27. 4. Altekruse SF, Lacey JVJ, Brinton LA, Gravitt PE, Silverberg S, Barnes, WAJ, Greenberg MD, Hadjimichael OC, McGowan L, Mortel R, Schwartz PE, Hildesheim A. Comparison of human papillomavirus genotypes, sexual, and reproductive risk factors of cervical adenocarcinoma and squamous cell carcinoma: Northeastern United States. Am J Obstet Gynecol, 2003; 188: 657663. 5. Green J, Gonzales AB, Sweetland S, Beral V, Chilvers C, Crossley B, Deacon J, Hermon C, Pha J, Mant D, Peto J, Pike M, Vessey MP Risk factors for adenocarcinoma and squamous cell carcinoma of the cervix in women aged 2044 years: the UK National Case Control Study of Cervical Cancer . British Journal of Cancer. 2003; 89: 2078 2086. 6. Vizcaino AP, Moreno V, Bosch FX, Munoz N, Barros-Dios XM, Parkin, DM. International trends in the incidence of cervical cancer: I. Adenocarcinoma and adenosquamous cell carcinomas. Int J Cancer. 1998; 75: 536545. 7. Brinton LA, Tashima KT, Lehman, HF, Levine RS, Mailin K, Savitz, DA, Stolley PD, Fraumeni JF. Epidemiology of cervical cancer by cell type. Cancer Res. 1987; 47: 1706-1711. 8. Moechherdiyantiningsih. Epidemiologi dan pengendalian kanker serviks. Medika. 2000 26; 3: 166-171. 9. American Cancer Society. 2008. Detailed guide: cervical cancer, what is cervical cancer?. Available from: <http://www.cancer.org/docroot/CDG/cdg_0.asp> [Accessed 24 November 2008] 10. Parsons L. & Sommers SC. Gynecology. Philadelphia:W.B Saunders Company. 1964 11. Wang SS, Sherman ME, Hildesheim A, Lacey JV & Devesa S. Cervical adenocarcinoma and squamous cell carcinoma incidence

11

trends among white women and black women in the United States for 1976-2000. American Cancer Society. 2004;100:1035-1044.