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ORIGINAL ARTICLE
Year : 2022 | Volume
: 18
| Issue : 6 | Page : 1530-1536
Survival pattern in cervical cancer patients in North West India: A tertiary care center study
Manjulata Yadav1, HS Kumar2, Rajesh Kumar1, Neeti Sharma1, Shankar Lal Jakhar3
1 Department of Radiation Oncology, Sardar Patel Medical College, Bikaner, Rajasthan, India
2 Department of Radiotherapy Acharya Tulsi Regional Cancer Treatment and Research Institute, Bikaner, Rajasthan, India
3 Department of Radiation Oncology, Acharya Tulsi Regional Cancer Treatment and Research Institute, Sardar Patel Medical College Bikaner, Rajasthan, India
Correspondence Address:
Manjulata Yadav
Senior Resident Department of Radiation Oncology, Acharya Tulsi Regional Cancer Treatment and Research Institute, Sardar Patel Medical College, Bikaner, Rajasthan
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/jcrt.jcrt_342_21
Background: Cervical cancer is most common malignancy of female reproductive system worldwide. As per GLOBOCAN 2020, there are 604,127 (6.5%) new cases of cervical cancer in the world, among women it is fourth most common and eighth most common in both sexes. In India,there are 123,907 total new cervical cancer cases (18.3% in female sex whereas 9.4% in both sexes). There are several etiological factors and the most significant is due to persistent infection of specific human papilloma virus (HPV) strains,particularly type 16 and 18 which are most common. Screening and early detection is likely to improve mortality and incidence also.
Aims and Objectives: The objective of this retrospective study was to determine the survival rates of cervical cancer and its associated factors in North-West region.
Materials and Methods: A total of 520 newly diagnosed cases of cervical cancer were enrolled at Acharya Tulsi Regional Cancer Treatment and Research Centre, Bikaner from January 1, 2014 to December 31, 2014 were included in this study. The main source of information was patient's medical records from which the data were abstracted and cases were followed up for next five years periodically from the date of diagnosis to access their survival status.
Results: Kaplan Meier analyses were conducted to identify overall survival and median survival time. Among 520 cases, 130 (25%) had lost to follow up so excluded from the study and the study sample was about 390 patients. The median survival time for cervical cancer in this study was 60 (32-60) months and the overall survival rates at 1, 3 and 5 years were 93.07%, 72.3% and 54.9% respectively. Education, use of oral contraceptive pills (OCP), tobacco chewing ( good survival in tobacco non-chewers) and staging were significantly associated with survival.
Conclusion: The 1, 3 and 5 year survival rates for cervical cancer were found to be 93.07%, 72.3% and 54.9% respectively. Various factors determining survival rates were potentially modifiable. Early diagnosis and prevention strategies are keys to obtain better outcomes.
Keywords: Cervical cancer, follow up, modifiable factors, survival
Cervical cancer is the most common malignant cancer of female reproductive organ worldwide. It is the fourth most prevalent cancer and also a leading cause of cancer death in women worldwide. As per the GLOBOCAN 2020, there are an estimated 19,292,789 total new cancer cases and 9,958,133 cancer deaths in the world. Among women, cervical cancer was fourth most common and eighth most common in both sexes, with 604,127 (6.5%) new cases in 2020 in the world.[1] Cervical cancer is ranked 8th in incidence and ranked 9th in mortality. In India, as per the GLOBOCAN 2020, it is estimated that there are 123,907 total new cervical cancer cases (18.3% in female cancer whereas 9.4% in both sexes).[2] The world age-standardized incidence (ASR) and mortality rates are 13.3/100,000 and 7.3/100,000, respectively. In India, it is estimated that there are 123,907 new cervical cancer cases (9.4%) with an ASR rate of 18.0/100,000 (higher than the rates observed in many other countries across the globe) and 77,348 cervical cancer deaths (9.1%) with a mortality rate of 11.4/100,000.[2] Women in their perimenopausal years are at high risk, and the peak incidence occurs mostly between the ages of 50 and 52 years. The two most common types of cervical cancer are squamous cell carcinoma and adenocarcinoma; between 80% and 90% of cervical carcinomas are squamous cell carcinomas. There are several etiological factors for cervical cancer, and the most significant is due to persistent infection of specific human papillomavirus (HPV) strains, particularly type 16 and 18 which are most common.
Molecular and human epidemiologic studies have demonstrated a strong relationship between HPV, cervical intraepithelial neoplasia, and invasive carcinoma of the cervix. HPV can be identified in more than 99% of cervical cancers, and infection with HPV is now accepted as a necessary cause of most cervical cancers.[3] The strong correlation between infection with HPV types and cervical cancer had led to the development of prophylactic HPV vaccine; randomized trials have consistently demonstrated these vaccines to be highly effective in preventing HPV infection.[4] In 2006, the U. S. Food and Drug Administration first approved a prophylactic HPV vaccine for women between the ages of 9 and 26 years.[4] Currently, three vaccines, Cervarix, Gardasil, and Gardasil 9, are available for use in the United States. Since HPV is a type of virus that is transmitted sexually, other known risk factors for cervical cancer are mostly related to sexual behavior. These include early age at marriage, early age at first sexual intercourse, more number of sexual partners, high parity, use of oral contraceptives, use of condoms during coitus, tobacco chewing and smoking, and immunosuppressed states such as human immunodeficiency virus infection.[5],[6],[7],[8] Cigarette smoking is the only nonsexual risk factor for cervical cancer and is associated with increased risk of squamous cell carcinoma.[9]
Survival refers to the life of a person after diagnosis of the disease. Oncogenesis is a long, time consuming complex process with various steps including changes at cellular, genetic, and epigenetic levels and abnormal cell division. This results in uncontrolled cell division and at the end normal cells turns into cancerous cells. Abnormal growing tissue or neoplasm can be in benign, potential malignant, or malignant status. With screening facilities as early the cellular changes are detected effective prevention or treatment strategies can be applied and outcome will improve. Conversely, when the cancer is detected at advanced stages of the disease, then there are chances of poor survival and low quality of life. People in rural areas generally have less access to healthcare than their urban counterparts. Fewer medical practitioners and healthcare facilities in these areas, less preventative care, lack of awareness and longer response times in emergencies. These all factors in rural areas can leads to difference in survival rates. Lack of awareness, inadequate screening facilities, diagnosis of cancer in advanced stages, and lack of access to affordable treatment[10],[11],[12] are the factors which indicate the low survival rate in our country. Treatment approach of cervical cancer depends on the stage, grade, histology of tumor, age of the patient, and related comorbidities.
> Materials and MethodsThe present study is a retrospective study comprising histological proven and newly diagnosed patients of cervical cancer over a period of 1 year (between January 1, 2014, and December 31, 2014). A total of 520 cases were newly registered in this time period, and out of them, 130 cases had lost to follow-up, and thus, 390 patients were considered as “eligible” for this study. Patients of cancer cervix who were registered prior to the study period and already on treatment were excluded from the study. The main source of information was the patient's medical records from which the data were abstracted. The Classification[13] for Site and Morphology and the Federation of Gynecology and Obstetrics (FIGO)[14] system for staging of disease were used. All patients underwent initial evaluation, staging work-up, histological confirmation, and joint multidisciplinary evaluation and treatment decision. All patients were treated as per their FIGO stages according to the National Comprehensive Cancer Network guidelines. Various modalities of treatment were used such as radiotherapy, chemotherapy, and surgery. Radiotherapy was prescribed in the form of brachytherapy and teletherapy, and the dose limits were also taken into concern. ECOG status ( Eastern Cooperative Oncology Group) Performance status helps to know general condition of patient. Score 0- Fully active, able to carry on all pre-disease performance without restriction 1- Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2- Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50%of waking hours. 3- Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours. 4- Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chairs. 5- Dead. This study was directed to identify various factors affecting survival so that policies makers can design the strategies for life prolongation. Factors such as treatment modalities and modality-wise survival were not taken into concern in this study. The patient characteristics including sociodemographic details, personal history, reproductive factors, tumor characteristics, diagnosis, and treatment details were compiled. Active follow-up was undertaken periodically if not then either telephonically or sending an e-mail to those who did not attend for follow-up. House visits were also undertaken for patients residing in Bikaner.
Data entry and statistical analysis
The collected data were transformed into variables and coded and entered in Microsoft Excel. Data were analyzed and statistically evaluated using the IBM Corp. Released 2017 . IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY USA : IBMCorp. 20-october-2020.
Quantitative data were expressed in mean ± standard deviation or median with interquartile range (IQR), whereas qualitative data were expressed in percentage, and statistical differences between the proportions were tested by Chi-square test or Fisher's exact test.
Kaplan–Meier analysis was conducted to identify overall survival rates and median survival time of the patients. Log-rank test[15] was used to compare survival rates between the groups. Multiple cox regression analysis was done to identify different factors associated with cervical cancer. P <0.05 was considered statistically significant.
> ResultsAll 390 patients of cervical cancer were analyzed in this study; their baseline general and clinical characteristics are shown in [Table 1]. The mean age at diagnosis was 52.37 ± 5.10 years (median age was 53 years, IQR: 49–55). Out of total 390 patients, 214 (54.9%) were alive and 176 (45.1%) were dead by the end of 5 years. Since 130 patients were lost to follow-up, so they were excluded from the study. Majority of patients were Hindus (77.7%), from rural areas (73.8%), from Rajasthan (57.4%), illiterates (51.0%), and married women (73.6%).
In the present study, survival rates at the end of 1, 3, and 5 years were higher in <50 or equal to 50 years' age group in comparison of older than 50 years' age group. Survival rates were higher in urban areas (95.1%, 74.5%, and 69.6%, respectively, at the end of 1, 3, and 5 years) than rural residents. Married women were showing good results (94.1%, 75.3%, and 60.3%, respectively) than widow and unmarried women. Education was a statistically significant factor (P < 0.01), and the 1-, 3-, and 5-year survival rates were 94.2%, 78.2%, and 70.7%, respectively, as shown by Kaplan–Meier survival curve in [Figure 1].
On basis of [Table 2] present study was showing women those were >50 years had poorest survival compare to < 50 or upto 50 years, proving an inverse relationship of age and survival. 1 year survival rates were better in Muslims and also in Others than Hindus, but this was not significant and later on 3 and 5 years survival rates were better for Hindus.
Rural, unmarried/widows, illiterate, nulliparous women were showing poor survivals. OCP users, tobacco non-chewers were showing good results for survival rares. Active or not bedridden patients with good ECOG (Eastern Cooperatve Oncology Group) were showing good survival rates. Place of residence was also not significant as 1 and 3 year survival were good in Rajasthani and Other groups patients, later on 5 year survival rates were good for Haryana and Other areas patients. but not significant. On basis of histology study was showing good results for squamous cell carcinomas ( squamous histology is radiosensitive), compare to adenocarcinomas and other histology
On the basis of [Table 3], the observed survival rates at the end of 1 year were 100%, 97.8%, 93.2%, and 75.7% for stage I, stage II, stage III, and stage IV, respectively. In the present study, the 3-year observed survival rates were 88.0%, 85.1%, 66.5%, and 48.6% for stage I, II, III, and IV and the 5-year observed survival rates were 84.0%, 73.8%, 47.7%, and 13.5% for stages I, II, III, and IV, respectively. In the present study, staging was a statistically significant factor (P < 0.01) and associated with survival, as shown by [Figure 2].
Figure 2: Survival on follow-up (at the end of 1, 3, and 5 years or 12, 36, and 60 months) by the stage of diseaseOn the basis of [Table 4], multivariate analysis of factors were showing that education, oral contraceptive pill (OCP) use, tobacco nonchewing, and stage of disease were statistically significant (P < 0.01) factors. In this study survival rates were better in women with age group upto 50 years, urban, married and multipara women than above 50 years, rural, unmarried or widows, nullipara. Patients who were presented in bedridden status represents less survival rates than active (not bedridden) status.
Table 4: Multivariate analysis of factors with prediction of mortality till the end of follow-up > Discussion Cervical cancer is one of the leading cancers among women in India, accounting for 123,907 (9.4%) new cases and 77,348 (9.1%) deaths annually. The incidence in Asian population was higher than that seen in other regions of the world.[16] The prevalence is higher in developing and underdeveloped countries and not so in the West.[17] The health infrastructure for early detection and treatment facilities in different populations has a direct impact on the global variations of cervical cancer. The survival of cervical cancer patients and indirectly the prognosis of the disease depend on a few independent variables. The major factors are stage, size, and histopathology of cancer, whereas the minor factors include the availability of effective prevention and treatment methods and various sociodemographic factors such as age, ethnicity, and sociocultural parameters.
Cervical cancer stages are determined by the International FIGO Staging System which categorized the cancer into stages according to tumor size. The FIGO Staging System has been the standard method in measuring the survival rates of patients as per their stages, where the higher cancer stage indicates the lower survival rate (American Cancer Society, 2013b). A study done by Chen et al.[18] reported a difference in survival rate of cervical cancer patients with different cancer histopathology types. Those with squamous cell carcinomas were reported to have higher survival rates as compared to patients with adenocarcinomas (66% and 63%, respectively).[18]
The CONCORD study based on 279 population-based cancer registries in 67 countries reported cancer survival of cases registered between 1995 and 2009.[19] The global 5-year survival was <40% and more than 70% indicating a wide range. In France, there was a decline in survival over the period which they attributed to intensive screening for preinvasive lesions, resulting in removal of less aggressive tumors;[20],[21] however, in Nordic countries, the survival was stable same or increased.[22] The CONCORD study reported that survival rates were >50% in many countries, except in Benghazi, Libya (39%), and Karunagappally, India (46%).
A similar study like the present study was conducted in Khon Kaen, Thailand, and reported by Sriamporn et al.[23] In this study, those who were aged <40 years had the best survival and those above 60 years had the poorest survival, proving an inverse relationship of age and survival, similar to the present study outcomes, that is, those <50 years to have better prognosis than those above the age of 50 years.
Similarly, a study done by Patil et al. in Nagpur stated that illiteracy was significantly associated with the risk of cervical cancer.[11] In a study done by Sankaranarayanan et al., the 5-year survival was 45.2% among the illiterates,[24] and comparable to the present study results.
In the present retrospective study, survival rates were better among the educated patients who had used OCPs and tobacco nonchewers and these factors were statistically significant. Staging was statistically significant as early stages give better treatment outcomes. Age at diagnosis, marital status, parity, and performance status at presentation were of significance for the outcomes in terms of survival. These variables are of prime importance and are taken into account for treatment management.
> ConclusionEducation, OCP use, tobacco nonchewing, and staging were significantly associated with survival rates. Early detection can improve the survival rate of cervical cancer. As many of the factors affecting survival are modifiable, efforts have to be made early through educational intervention regarding the risk factors for cervical cancer to the adolescent age groups through School Health Programmes, community awareness through women Self-Help Groups/Mahila Mandals, and also through mass media to the general public. Efforts should be made to provide accessible and affordable diagnostic and treatment facilities for cervical cancer.
Declaration of patient consent
The Institutional Review Board permission was obtained for the study.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
> References
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