ULUSLARARAS HEMATOLOJI-ONKOLOJI DERGISI ARTICLE International Journal of Hematology and Oncology

Risk Factors for Cervical Cancer: Results from a

Hospital-Based Case-Control Study

Nesrin REIS1, Nezihe K. BEJI2, Dilek KILIC3

1
Bezmialem Vakf University, Faculty of Health Sciences, Department of Obstetric and Gynecologic Nursing, Istanbul
2
Istanbul University, Florence Nigtingale College of Nursing, Department of Obstetric and Gynecologic Nursing, Istanbul
3
Atatrk University, Faculty of Health Sciences, Department of Community Health Nursing, Erzurum, TURKEY

ABSTRACT

The aim of this study was to investigate risk factors for cervical cancer in Turkish women. In a hospital-based case-control study
in stanbul, 209 patients with histologically confirmed cervical cancer were compared with 1050 controls, who were admitted to
the different departments of the same hospital. Odds ratios (OR) and 95% confidence intervals (CI) were obtained from multiva-
riate logistic regression analysis, fitted by the method of maximum likelihood.
Risk factors for cervical cancer were found to be early age at first sexual intercourse (OR = 58.07, 95% CI: 27.88-120.95) and
history of genital infection (OR = 5.17, 95% CI: 3.51-7.60). However, compared with controls, it was found that cases including
higher education (OR = 0.18, 95% CI: 0.10-0.30), non-married (OR = 0.07, 95% CI: 0.04-0.12) and non-use of alcohol (OR =
0.30, 95% CI: 0.14-0.65) had a decreased risk for cervical cancer.
Our results are supportive of the hypothesis that early age at first sexual intercourse and history of genital infection is rela-
ted with the risk factors for cervical cancer. Therefore, monogamy, late commencement of sexual activity, personal hygiene
and use of barrier contraceptive methods help towards primary prevention.

Keywords: Cervical cancer, Risk factors

ABSTRACT

Servikal Kanser in Risk Faktrleri: Hastane Temelli Vaka-Kontrol almasnn Sonular

Bu aratrmann amac, Trk kadnlarndaki servikal kanser risk faktrlerini belirlemektir. stanbulda yrtlen hastane temelli
vaka-kontrol almasnda, histolojik olarak servikal kanser tans konulmu 209 hasta, ayn hastanenin farkl blmlerine
bavuran 1050 kontrol grubuyla karlatrld. Greli risk oranlar (ORs) ve %95 gven aral (CI), maksimum benzerlik meto-
duyla uygunluu salanan, ok deikenli lojistik regression analizinden elde edildi. Servikal kanser iin risk faktrleri, erken
yalarda ilk cinsel iliki (OR = 58.07, 95% CI: 27.88-120.95) ve genital infeksiyon yks (OR = 5.17, 95% CI: 3.51-7.60)
olarak bulundu. Buna ragmen kontrol grubuyla karlatrldnda, yksek eitim (OR = 0.18, 95% CI: 0.10-0.30), evli olma-
ma (OR = 0.07, 95% CI: 0.04-0.12) ve sigara kullanmama (OR = 0.30, 95% CI: 0.14-0.65), servikal kanser iin azaltc risk
faktr olarak belirlendi.
Aratrma sonucu, erken yata ilk cinsel ilikinin ve genital infeksiyon yksnn servikal kanser iin risk faktr olduunu
gstermektedir. Bu nedenle primer korunmada tek elilik, seksel aktivitenin uygun yata balatlmas ve bariyerli kontraseptif
yntem kullanm nemlidir.

Anahtar Kelimeler: Serviks kanseri, Risk faktrleri

UHOD Number: 3 Volume: 21 Year: 2011 doi: 10.4999/uhod.09061 153

INTRODUCTION studies and publications in other countries, we are
Cervical cancer is second only to breast cancer as the not aware of any earlier investigation into risk factors
most common female malignancy in both incidence for cervical cancer carried out in our country. There-
and mortality worldwide.1 More than 200,000 deaths fore, the present study was carried out in order to de-
due to it are registered each year, predominantly termine the risk factors leading to cervical cancer in
among economically disadvantaged women in both Turkish women.
developing and industrialized nations.2 Some of the
worlds highest rates are from sub-Saharan Africa, MATERIAL AND METHODS
including South Africa (40/100.000). In Africa, most
Between September 2002 and October 2003, we con-
patients with cervical carcinoma present with late
ducted a case-control study of cervical cancer. Cases
stage disease (59.3% stage III vs. 5.2 % stage 1B).
included 209 women with a histologically confirmed
While a decline in incidence and mortality from cer-
diagnosis of cervical cancer, who were admitted to
vical cancer has been documented in first world co-
the Breast and Gynecologic Policlinic of Oncological
untries such as the United States, Canada, and Scan-
Institute of Istanbul University in Istanbul. Between
dinavia, this trend is not apparent for most develo-
these dates, we visited the outpatient clinic of the
ping countries due to lack of or inefficient screening
hospital every two days of the week (Monday and
programs.3 It is hardly possible to present proper and
Wednesday), and interviewed with 209 women who
updated data concerning Turkey due to the insuffici-
applied to the clinic and agreed to participate in the
ency of the statistical records. According to the data
study.
of the year 2008, the incidence in Turkey is 4.2 per
100.000.4 Controls were women residing in the same geograp-
hical regions, and they were admitted to the wards or
Various agents have been reported either as an asso-
outpatient clinics of the different departments of the
ciation or cause of cervical cancer. These include eth-
same university's hospital during the same interval.
nic factors, number of partners, and age at first sexu-
In between these dates, we visited the ward and out-
al intercourse, age at first birth, steroid contracepti-
patient clinics every two day of the week (Thursday
on, and infectious agents such as human papilloma-
and Friday) and a total of 1050 women were intervi-
virus (HPV), herpes simplex virus type 2 and
ewed. Half of the controls had no disease (%50) and
Chlamydia trachomatis, among others.3,5 As HPV in-
they were the relatives of the patients accompanying
fection is considered a sexually transmitted disease,
them during their stay at hospital. The others had an
investigations to reveal sexual behavioral risk factors
orthopedic disease, surgical (eye disease) or miscel-
have been conducted.6,7 Overall, women who had
laneous illnesses, such as disorders of the ear, nose
first sexual intercourse at an early age or who have
and throat. Women who had a malignant, endocrine,
had many sexual partners have an increased risk of
or gynecologic disease were not included in control
developing cervical cancer. Apart from sexual beha-
group. In addition, none of the relatives of the pati-
vior, smoking, nutrition, parity and oral contracepti-
ents applying to the oncology department were ad-
ve use have been reported as major environmental
mitted to the control group.
risk factors for cervical cancer.5,8 However, to date,
there has been no clear-cut proven evidence of a bi- Ethics: After Institutional Review Board approval
ologic basis for these agents and the incidence of cer- had been obtained, data were collected. All the parti-
vical cancer varies greatly from one population to cipant patients gave their informed consent, and if
another, depending on the prevalent risk factors they prefered not to continue, they could withdraw
mostly influenced by lifestyle.2,5,9 These factors are from the study any time they wish. Also, the cases
well established in many countries. and controls were told that their decision of whether
to participate in the research would not affect the he-
Awareness of the risk factors believed and known to
althcare services given to them and their patients,
lead to cervical cancer is quite significant for preven-
and none of the participants (cases and controls) re-
ting the illness, for detecting the groups with risk and
fused the interview.
for the early diagnosis.10,11 Although our literature re-
view has shown there are a lot of epidemiological

154 UHOD Number: 3 Volume: 21 Year: 2011

Data Collection: Trained study staff interviewed feeding, age at menarche, oral contraceptive and
both case patients and control subjects, and all inter- HRT use, age at first sexual intercourse, sexual part-
views were conducted in hospitals and interviewed ner, genital infection to find their associated with cer-
the subjects who agreed to take part in the study we- vical cancer. This analysis was used Chi-square. La-
re interviewed. Interviews with the case group were ter these variables that are related with cervical can-
made at the oncology clinics where they come for cer were examined to figure out which variables inc-
their routine medical check-ups and at a suitable ro- rease or reduce the risk factor for cervical cancer.
om after the control. The cases were given enough ti-
me for each interview. Similarly, the interviews of
RESULTS
the control group were made at a suitable place and
in an adequate period. Table 1 presents the distribution of 209 cervical can-
cer cases and 1050 controls according to age and se-
Data were collected through questionnaire. The qu-
lected general characteristic variables. Table 2 gives
estionnaire consisted of questions related to demog-
the distribution of cervical cancer cases and controls
raphic characteristics (age, education, marital status,
according to reproductive history and menstrual fac-
body mass index, chronic diseases, smoking and al-
tors. As for the distribution of cases and controls ac-
cohol), menstrual and reproductive history (parity,
cording to sexual history, it is presented in Table 3.
age at first birth, breast-feeding, age at menarche,
Table 4 presents also the results of multivariate logis-
oral contraceptive and hormone replacement therapy
tic regression analyses.
(HRT) use, and sexual history (age at first sexual in-
tercourse, sexual partner, genital infection). Body Compared with the age at first sexual intercourse of
mass index (BMI) was calculated as weight (kg) / he- above 21 years, age at 16 or less increased the risk
ight (m2), according to Quatelets formula. Parity was (OR = 58.07, 95% CI: 27.88-120.95). Overall, wo-
the number of full-term pregnancies, which were de- men who ever had sexually transmitted tract repro-
fined as pregnancies longer than 6 months regardless ductive infection (neisseria gonorrhoeae, chlamydia
of the outcome. HRT use was categorized as follows: trachomatis, etc) had an OR of cervical cancer of
never users (none or less than 6 months of cumulati- 5.17 (95% CI: 3.51-7.60) compared with non-repro-
ve use), and current users (at least 6 months of use ductive infection. However, However, compared
within previous 12 months before the reference da- with controls, it was found that cases including hig-
te). Analysis according to the type of therapy (estro- her education (OR = 0.18, 95% CI: 0.10-0.30), non-
gen alone or estrogen combined with progesterone) married (OR = 0.07, 95% CI: 0.04-0.12) and non-
was not presented due to small sample size. Hyper- use of alcohol (OR = 0.30, 95% CI: 0.14-0.65) had
tension or diabetes was registered if a woman repor- a decreased risk for cervical cancer.
ted treatment for the condition or said that it had be-
en diagnosed by a physician. A woman was conside-
DISCUSSION
red a smoker if she had smoked at least one cigaret-
te/day for at least one year. In the group of cases, fo- Most women who develop cervical cancer tend to ha-
ur women knew that they were infected with HPV, ve one or more identifiable factors that increase the-
HSV. However, why the others did not know and we- ir risk for the disease. These include ethnic factors,
re not sure that the similar infections were diagnosed number of partners, and age at first sexual intercour-
in themselves, they did not insert in statistical analyzes. se, age at first birth, steroid, contraception, and infec-
tious agents such as human papillomavirus (HPV),
Statistical Analysis: Data about all the risk factors
herpes simplex virus type 2 and Chlamydia tracho-
were entered into an SPSS 10.0 for Windows com-
matis, among others.3,5 Apart from these, smoking,
puter program. We modeled the probability of dise-
nutrition, parity and oral contraceptive use have been
ase by means of the following logistic regression mo-
reported as major environmental risk factors for cer-
del.12 The statistical analysis of the study was evalu-
vical cancer.5,8 However, there has been no clear-cut
ated with regard to 16 variables in age, education,
proven evidence of a biologic basis for these agents
marital status, body mass index, chronic diseases,
and the incidence of cervical cancer varies greatly
smoking and alcohol, parity, age at first birth, breast-
from one population to another.2,5,9 In this study; edu-

UHOD Number: 3 Volume: 21 Year: 2011 155

 Table 1. Distribution of cases and controls according to age and selected general characteristics

Factor Cases Controls X2 p

(n=209) (n=1050)

Age
49 91 (48.5) 560 (53.3)
50-59 51 (24.4) 260 (24.8) 10.858 0.004
60 67 (32.1) 230 (21.9)
Education
Illiterate 52 (24.9) 168 (16.0) 30.822 0.001
Literate+Primary school 104 (49.8) 730 (69.5)
Secondary school+Higher education 53 (25.3) 152 (14.5)
Marital status
Ever married 153 (73.2) 989 (94.2) 91.058 0.001
Never married 56 (2.8) 61 (5.8)
Body mass index
Normal (18.5-24.99) 77 (36.8) 291 (27.8) 6.976 0.008
Obese (25.0 ) 132 (63.2) 758 (72.2)
Chronic illnesses
No 148 (70.8) 821 (78.2) 5.351 0.020
Diabetes+Hypertension 61 (29.2) 229 (21.8)
Smoking
Never 149 (71.3) 841 (80.1) 8.040 0.004
Ever 60 (28.7) 209 (19.9)
Alcohol
Never 187 (89.5) 1004 (95.6) 12.884 0.001
Ever 22 (10.5) 46 (4.4)

cation, marital status, use of alcohol, age at the first studies showed that cervical cancer increased in wo-
sexual intercourse and history of genital infection men who gave birth to their first child at an earlier
were found to be associated with cervical cancer. age.
In population-based case-control studies, Parikh et In epidemiological research it was reported that ciga-
al.9 and Gawande et al.13, found illiteracy as a factor rette smoking and use of alcohol are an increased risk
associated with cervical cancer. Similarly, In our of developing cervical cancer.14,18 According to our
study, It was found that higher education had a dec- study results, non-use of alcohol had a decreased risk
reased risk for cervical cancer; the OR being 0.18. for cervical cancer, the OR being 0.30, which was
Presumably, decreased educational level causes an parallel with other study results.19,20,21 Sikstrom et al.22
increase in intercourse at an early age, sexual partner reported that smoking, alcohol and drug abuse are
and poor genital hygiene. risk markers for cervical human papillomavirus in-
We found that non-married had a decreased risk for fection. However, there are some studies that could
cervical cancer; the OR being 0.07. Therefore, our not find such a relationship.8,23 Today, the life style of
study confirmed that reproductive history of woman Turkish women is changing. They predispose to use
is associated with risk factors for cervical cancer. of alcohol and cigarette and these changes are stri-
Atalah et al.14, Bjorge and Kravdal15,Yoo et al.16 re- king for the finding that use of alcohol and cigaret-
ported that early age at first full term pregnant was te smoking are risk factor for cervical cancer.
associated with risk factors. However, there is a The association between sexual history and cervical
study that could not find such a relationship.17 These cancer is well established. Coitus-related behaviors,

156 UHOD Number: 3 Volume: 21 Year: 2011

 Table 2. Distribution of cases and controls according to reproductive history and menstrual factors

Factor Cases Controls X2 p

(n=209) (n=1050)

Parity
2 81 (38.8) 527 (50.2) 9.127 0.002
3 128 (61.2) 523 (49.8)
Age at first birth
20 147 (70.3) 502 (47.8) 28.575 0.001
21-29 54 (25.9) 446 (42.5)
30 8 (3.8) 102 (9.7)
Breast-feeding
(At least 1 year)
Yes 177 (84.7) 883 (84.1) 0.046 0.829
Never 32 (15.3) 167 (15.9)
Age at menarche
12 58 (27.8) 176 (16.8) 14.600 0.001
13-14 117 (56.0) 648 (61.7)
15 - 34 (16.2) 226 (21.5)
Oral contraceptive use
Ever 58 (27.8) 154 (14.7) 25.951 0.001
Never 117 (56.0) 896 (85.3)
HRT use
Ever 61 (29.2) 58 (5.5) 6.066 0.014
Never 148 (70.8) 992 (94.5)

such as early age at first intercourse and multiple se- sexual activity is an important prevention in our co-
xual partners have been found to be associated with untry that has married and the first sexual intercour-
cervical cancer.11,19,20,24-26 In our study, compared with se at early age.
women in late age at first intercourse, women in the Case-control studies have generally reported positive
early age had a higher risk for cervical cancer. Sier- associations between history of genital infection such
ra-Torres2, Turkistanli11, Yoo et al.16, Liu et al.19, Pet- as neisseria gonorrhoeae, chlamydia trachomatis and
tifor et al.24, Biswas et al.25, have also determined re- cervical cancer.7,9,19,22,25 Our study confirmed that his-
sults in conformity with those of ours. Therefore, our tory of genital infection is an increased risk of deve-
results and other studies support the common idea loping cervical cancer. In parallel to our studys re-
that early age at first intercourse increases the risk. sults, there are some case-control studies that repor-
In our study, multiple sexual partners were not found ted positive associations between history of genital
to be associated with cervical cancer. But most other infection and cervical cancer. Predisposition to such
studies2,11,20,24, the increased number of sexual partners history of genital infection puts Turkish women in a
increased cervical cancer risk compared with fewer high-risk group for cervical cancer. Therefore, wo-
number of sexual partners. One other study19 also fo- men are emphasized that personal hygiene and use of
und that the mean cervical cancer age of the Chinese barrier contraceptive methods help towards primary
was significantly lower than the Australians (44 ver- prevention in our country.
sus 53 years), because of multiple sexual partners The results from the current study must be conside-
and history of sexually transmitted diseases. The re- red in light of certain limitations. Firstly, the study
sults support the hypothesis that multiple sexual part- was carried out in a small group of 209 subjects for a
ners play a role in cervical carcinogenesis. Accor- year. Another limitation of the study is that all data
ding to results of the study, late commencement of

UHOD Number: 3 Volume: 21 Year: 2011 157

 Table 3. Distribution of cases and controls according to sexual history

Factor Cases Controls X2 p

(n=209) (n=1050)

Age at first sexual intercourse

16 80 (38.3) 91 (8.7) 167.243 0.001
17-20 105 (50.2) 466 (44.3)
21 24 (11.5) 493 (47.0)
Sexual partner
1-2 192 (91.9) 1035 (98.6) 31.639 0.001
3 17 (8.1) 15 (1.4)
Genital infection
Yes 136 (65.1) 264 (25.1) 128.199 0.001
No 73 (34.9) 786 (74.9)

were obtained from the womens self-reports. All 5. Shields TS, Brinton LA, Burk RD, et al. A case-control
these data may not be true. For some of the questions study of risk factors for invasive cervical cancer among
U.S. women exposed to oncogenic types of human
were too difficult for them to remember: i.e. preg-
papillomavirus. Cancer Epidemiol Biomarkers Prev 13:
nancy cases resulting in dead births, the age of me- 1574-1582, 2004.
narche, age at the first sexual intercourse and story of 6. McFadden SE, Schumann L. The role of human papil-
HPV and HSV. However, the findings and limitations lomavirus in screening for cervical cancer. J Am Acad
of the study are quite useful in that they illuminate Nurse Pract 13: 116-125, 2001.

the progressive research in this field. 7. Gopalkrishna V, Aggarwal N, Malhotra VL, et al.
Chlamydia trachomatis and human papillomavirus in-
In conclusion, our results are supportive of the fection in Indian women with sexually transmitted dise-
hypothesis that history of early age at first sexual ac- ases and cervical precancerous and cancerous lesi-
tivity and genital infection are risk factors for cervi- ons. Clin Microbiol Infect 6: 88-93, 2000.
8. Juneja A, Sehgal A, Mitra AB, Pandey A. A survey on
cal cancer. Therefore, monogamy, late commence-
risk factors associated with cervival cancer. Indian J
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158 UHOD Number: 3 Volume: 21 Year: 2011

 Table 4. The results of multivariate logistic regression analyses

Factor p OR (95% CI)

Education
Illiterate (reference) 1
Literate+Primary school 0.001 0.13 0.07 0.24
Secondary school+Higher education 0.001 0.18 0.10 0.30
Marital status 1
Ever married (ref: no) 0.001 0.07 0.04 0.12
Never married
Alcohol 1
Ever (ref: no) 0.002 0.30 0.14 0.65
Never
Age at first sexual intercourse 1
21 (ref: no) 0.001 17.69 9.22 33.93
17-20 0.001 58.07 27.88 120.95
16
Genital infection 1
No 0.001 5.17 3.51 7.60
Yes

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UHOD Number: 3 Volume: 21 Year: 2011 159