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A study to assess select risk factors for carcinoma cervix among patients attending Kidwai Memorial Institute of Oncology

The burden of non-communicable disease is increasing due to increasing life expectancy, change in life style and behavioral pattern of people and improved medical care. The burden of cancer is distributed unequally between developed and developing countries, with particular cancer types exhibiting different patterns of distribution. According to WHO estimates for 2011, cancer now causes more deaths than all coronary heart disease or all stroke. 1 ABSTRACT

Cervical cancer is the second most common female cancer in women aged 15 to 44 years and fourth most common cancer in women in the world, with an estimated 528,000 new cases and 266,000 deaths, accounting for 7.5% of all female cancer deaths in 2012 (Globocan, 2012). In developed countries Age-standardized Incidence and Mortality Rates is 9/100,000 and 3.2/100,00 for developing countries it is 15.7/100,000 and 8.3/100,000. 2 More than 85% of these cases and deaths occur in developing countries where as in affluent countries, cancer cervix does not find place even in top five cancers in women. 3 The disproportionately high burden of cervical cancer in developing countries and elsewhere in medically underserved populations is largely due to a lack of screening that allows detection of precancerous and early stage cervical cancer. 4 Cervical cancer ranks second among the female cancers in India. India bears one-third of the World's burden of Cervical Cancer. The incidence of cervical cancer for the year 2012 in India was 123,000, and mortality was 67,000. 2 The age standardized incidence rate for cancer cervix in India is 27/100,000 population and mortality rate being 15.2/100,000 and DALYs lost is 431,538. In Bangalore PBCR cancer cervix was the second leading site accounting for about 12.3% of cancer in females, leading site being Breast (27.5%). The age adjusted incidence rate for cancer cervix was 15.3/100000 population. 5 Risk factor for development of cancer cervix includes human papilloma virus (HPV) infection which has been established as the necessary, but not solely sufficient, cause of cervical cancer. 6 Majority of women though infected with an oncogenic HPV type never develop cervical cancer, which suggests that additional factors acting in conjunction with HPV influence the risk of disease development, hence the objective of the study was to assess the association between select risk factor and cancer cervix among patient attending Kidwai Institute of Oncology.

METHODS
An age group matched case -control study was carried out at Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India from February 2011 to May 2012. The institutional Ethical clearance was obtained. Kidwai Memorial Institute of Oncology which is a Regional cancer centre for Karnataka. Necessary permission was sought from the concerned authorities in Kidwai Memorial Institute of oncology.
Cases were newly diagnosed and histologically confirmed cases of cervical cancer, above 30 years of age, attending Kidwai Memorial Institute of Oncology Bangalore. One control was selected for each case (1:1 ratio), the cases and controls were group matched for age (±5 years), and controls were apparently healthy hospital attendees (relatives, friends and other visitors).

Inclusion criteria
Histologically confirmed newly diagnosed cases of squamous cell carcinoma of cervix, above 30 years of age including all stages of the disease, who were willing to participate in the study. No previous treatment for any kind of malignancy.

Exclusion criteria
Patient diagnosed with other gynecological problems and cancers (i.e., vagina, vulva, cancer of endometrium, ovary and breast) adenocarcinoma of cervix, and individuals who are not able to respond coherently to the question asked. Controls were excluded if they had undergone hysterectomy.
Sample size was calculated using N master, the study by Silvia et al was used as reference to calculate sample size. 6 Proportion of cases and controls with respect to age at 1 st intercourse was taken, with alpha error of 10% and 80% power; the sample size was calculated to be 190 each for cases and controls.
A predesigned semi structured questionnaire was developed and pilot tested. The study subjects were selected from the Department of Radiotherapy, patients were informed about the study objectives and invited to participate, all cases were histologically confirmed and then included in study, and informed written consent was taken from both the cases and controls. Semi-structured questionnaire was administered to both cases and controls and information regarding the socio-demographic factors, reproductive and sexual history, smoking and hygiene were collected.

Statistical analysis
The data was entered in excel and analysis was done using SPSS software version 18.0, all the quantitative variable such as age, parity etc, is summarized in terms of mean, median, etc; to understand the variation with the quantitative variable standard deviation is calculated. The strength of association for various risk factors between cases and controls was estimated using odds ratio with 95% confidence interval and p<0.05 was considered for statistical significance. To evaluate the independent risk factor associated with the development of carcinoma cervix, backward multiple logistic regression analysis was performed.

RESULTS
The study included 200 cases of cancer cervix and equal number of apparently healthy controls.

Medical information
All the cases were squamous cell carcinoma of cervix. Among the cases 109(49.5%) of them presented to    [6][7][8] The education status among the groups were compared it was seen that the 139 (69.5%) of the cases were not literate compared to 73 (36.5%) of controls, the odds of cancer cervix was 3.9 folds (95% C.I 2.9-5.7) more among the not literate compared to literate, which was statistically significant similar results were found in study done in Chennai with odds of 4.8 for cervical cancer (illiterate vs. literate) and other studies. 6,[9][10][11][12] In a metanalysis by Parikh et al it was found that non literate women were at higher risk of cervical cancer. 13

Marital status and reproductive factors
In this study the married subjects were compared with widow, separated and divorced and these are mentioned as others, the odds of cancer cervix was 1.7 (95% C.I 1.2-2.6) times higher among others as compared to married subjects, that was statistically significant, similar finding were found in Francheschi et al study done in Chennai, the odds was 8.3 (95% C.I 4.2-17.6) for widowed. 6,14 Age at consummation of marriage, (<18 years vs. >18 years) the odds was 5.9 times (95% C.I 2.6-19.4) more among women less than 18 years which was statistically significant, similar finding were found in Biswas et al, a meta-analysis also revealed the similar findings. 6,8,15 Age at 1 st pregnancy, among the cases 92 (46.2%) and controls 35 (18%) were 1 st time pregnant less than 18 years of age, the odds was 3.9 (95% C.I 2.8-5.9) time more among those who had 1 st pregnancy(<18 years vs. ≥18 years) that was statistically significant. A study in Chennai reported the odds of cancer cervix was 1.1, 2.2 respectively for age at pregnancy at 17-18 years and <17 years as compared to >18 years, a meta-analysis also revealed similar results. 6,16,17 Number of live births was considered as one of the risk factor and analysed, the study showed odds of 2.9 (95% C.I 1.7-5.8) time more risk of cancer cervix among women with >5 live births compared to 0-5 live births, statistically significance obtained. A hospital study showed odds of 5.7 compared to 1-2 births, similar results were also found in other studies. 6,16,18,19 Genital and menstrual hygiene

Material used during menstruation
This study revealed that still many study subjects 332 (83%) used cloth as material during their menstruation. Among case 188 (94%) used cloth compared to 144 (72%) among controls, the odds of cancer cervix was six folds higher among cloth users compared to those using sanitary pads (95% C.I 3.

Sex during menstruation
Most of the study subjects did not practice sex during menstruation, the odd of cancer cervix was 3 folds higher

Tobacco use
The odds of cancer cervix was 3.4 (95% C.I 2.2-5.6) times for those who consumed tobacco of any form compared to those who did not use, similar results are shown in a study done in Philippines, Thailand and Utah. 24,25 The factors which showed statistical significance at p≤0.05 in univariate analysis were considered for multiple logistic regression to check for independent association, which reveled factors like that early age at pregnancy, poor menstrual and genital hygiene as risk factors for cancer cervix.

CONCLUSION
The data shows that early pregnancy, poor menstrual and genital hygiene as risk factors for cancer cervix, and the above mentioned risk factors are highly amenable for primary prevention.

Limitations
 Investigator bias: could not be eliminated completely as the investigator was not blinded to the cases and controls, but the time duration for interviewing both the case and control has been same.  Referral Bias: The cases and controls were selected from a single hospital but the hospital where the study was carried out is comprehensive and regional center for cancer research and treatment in Karnataka. Patients from all over Karnataka as well as from adjoining areas of the neighboring states and other regions attended the hospital.  In this study cases and controls were not tested for HPV, however this would not pose a problem as HPV as already been considered as the necessary cause, hence other risk factors have been analyzed in this study.  In this study controls were not confirmed by any diagnostic test for not having cancer cervix, however only apparently healthy females were included, without any history of any prior or present gynecological problem.  The conformation for the presence of Sexually transmitted disease was done on the basis of syndromic approach alone without any investigations..