Context Carcinoma Cervix is one of the leading prevalent cancers in India especially in rural population and causes a significant mortality. WHO has launched many projects for prevention, screening and treatment plans. Even after many projects, Cervical Cancer persists as a heavy burden public health problem in rural India.
Aims To calculate survival of cancer cervix patients in a rural population-based RCC and to discuss the factors affecting it.
Methods and Material A hospital-based gathering of retrospective data of the patients diagnosed with carcinoma cervix over 5 years from January 2013 to December 2017 (single institution analysis). We included 751 patient’s data from our cancer registry for analysis. Data related to demographics, treatment and follow up records were taken and statistical analysis done.
Results The survival rates were 64.0%, 50.0%, 36.9% and 17.5% for Stage I, Stage II, Stage III and Stage IV, respectively. The best survival outcomes were for those treated with only surgery. Involvement of nodes had poor survival than those with no involvement. Various patient-related factors like Religion, Education and Marital status are found to be non-significant factors even-though they have survival differences. STAGE of the disease emerged as a significant prognostic factor.
Conclusion Our study concluded that higher stage and nodal involvement had poor outcomes and also lower survival compared to Western and Indian literature. We should also address all the socio-economic factors that affects survival. Randomized prospective studies are needed to evaluate the effect of socio-economic factors on survival.
Keywords : Cervical cancer · Rural · Socio-economic · Stage · Survival
According to GLOBOCAN 2020, nearly 604,100 new cases
of Cervical Cancer are diagnosed every year and around
341,831 patients die due to the disease every year [1]. In
India around 1.2 lakh new cases of cervical cancer are diagnosed
every year which accounts for one-fifth of the global burden [2]. Around 77,000 people die every year due to
cervical cancer in India. It accounts for 9.5% of all cancers
diagnosed in India every year [2].
It is one of the leading cancers in women and also a
leading cause of mortality especially in rural populations.
This is because the majority of the rural population are
unaware of screening methods and HPV vaccination, poor
sexual practices, poor access to health care, and late diagnosis
leading to treatment failure. Elderly people and people
with low socio-economic status are vulnerable groups
for developing cervical cancer but it is still controversial
how they interact with these factors and which of these
factors have a huge impact on screening, diagnosis, and
survival of patients [3]. Various risk factors commonly
encountered in the rural population are early age marriage,
early age of sexual intercourse, poor sexual practices
and multiple sexual partners, early age pregnancy,
etc., and all these lead to increased risk of HPV infection
among them which in turn leads to increased risk of cervical cancer. 70% to 75% of cervical cancers are due to
high-risk HPV subtypes 16 and 18. Several cofactors have
been identified that may contribute to the development of
HPV carcinogenesis. These include smoking, high parity,
and coinfection with other sexually transmitted diseases.
The development of HPV vaccines is based on this strong
causative factor and association between high-risk HPV
subtypes and cervical carcinoma. So, in 2014, WHO concluded
that immunologic evidence was sufficient to recommend
a schedule of two doses administered with at least a
6-month interval to girls younger than 15 years old. Even
after WHO recommendations and multiple health projects,
the existence and clinical use of HPV vaccination in rural
populations is subtle and doesn't change the rates of cervical
cancer in rural populations.
Squamous cell cancer is the predominant subtype followed by adenocarcinoma. Other histological subtypes are rare constituting less than 3%. The prognosis of rural patients tends to be poorer than urban population. The two important reasons for this are lack of access to standard health care and advanced-stage diagnosis. This inequality in cancer survival between and within countries is largely due to the differences in awareness about sexual practices and risk of cervical cancer, availability of screening practices, socio-economic and cultural factors, and accessibility to tertiary cancer institutes, diagnosis, and treatment [4]. Latestage diagnosis and delay in treatment of cervical cancer results in poor survival outcomes in low-resource settings, even though it is a preventable one [5]. We all know the FIGO stage directly correlates with prognosis. So early diagnosis is important in improving the survival of the patient. Considering all these factors, we did a retrospective analysis of all cancer cervix patients in our institute by collecting data from our cancer registry. We describe in this study the incidence, demographics related to patient and tumor factors, and survival outcomes.
751 Cancer Cervix cases are included in our analysis. The
most common age group affected are 40–60 years. Characteristics
of Age distribution, Marital status, Religion,
and Education are illustrated in Table 1. It clearly explains
that around 24% of our treated population is widowed,
which causes various difficulties in undergoing treatment
and follow-up and there indirectly affects survival. Similarly,
Education of the patient can affect survival indirectly
through cultural and sexual practices, attitudes, beliefs, and
the importance of all forms of treatment and adherence to
follow-up.
Squamous cell carcinoma is the most common histology
which constitutes about 88.9% of cases followed by adenocarcinoma-
9.7%, small cell carcinoma-0.26%, and other rare
histologies-1.19%.
The most common Stage of presentation in our analysis is II B (n = 196, 26%) followed by III C1 (n = 148, 19.7%) and III B (n = 137, 18.2%). The detailed distribution of individual stages is represented in Table 2. But as a whole, FIGO stage 3 patients are higher (n = 385, 51.3%) compared to stage 2 patients (n = 228, 30.4%) concerning the stage-wise distribution of cervical cancer patients. Locally advanced cases are most-commoner in our institution which in turn affects overall survival.
Patients were treated based on their performance status, Stage at presentation, and as per MDT decision. Patients have undergone either single-modality treatment or multimodality treatment. Concurrent Chemo-Radiation is the most common treatment given since the majority of cases are locally advanced cases (n = 460, 61.3%) followed by radiotherapy alone (n = 217, 28.9%). Surgery with or without adjuvant treatment is given for 52 patients (6.92%). Kaplan–Meier analysis (Fig. 1) based on various modalities of treatment given shows that patients treated with surgery alone have the highest survival (early cases) followed by surgery with or without adjuvant treatment (early cases with high-risk features) followed by concurrent chemoradiation (locally advanced cases). Patients treated with chemotherapy alone have the least survival (metastatic disease). This concluded that treatment based on stage is the independent prognostic factor for survival.
Survival drops as the stage increases. But in our analysis, a notable difference is, survival is low for all stages (stage 1 -64%, stage 2–50%, stage 3–36.9%, stage 4–17.5%-Table 3) compared to a standard study from TATA memorial hospital, India (stage 1– 83.5%, stage 2–80.6%, stage 3–66%, stage 4–37.1%). Also, survival from our institute is low compared to Western literature-SEER data (stage 1–92%, stage 2- 84%, stage 3–58%, stage 4–18%). This difference in survival can be attributed to various other factors like socioeconomic status, the patient's geography (rural or urban), the patient's general condition and nutrition, adherence to treatment protocol and follow up and finally advances in treatment modalities. All these factors lack in many of the rural population-based cancer centers in our country leading to diminished survival rates compared to standard literature. Figure 2, Kaplan–Meier curves on survival demonstrating significant survival differences based on stage. This again confirms stage of the disease is the most independent predictor for survival. Our findings are similar to a study conducted by Ganesh Balasubramaniam et al [6].
Multivariate analysis for overall survival of Education, Religion, Marital status, and FIGO stage was done (Table 4). With regards to the education and marital status of patients, there is no significant survival difference but the FIGO stage (p-value < 0.008) and histological subtype (p-value = 0.04) have significant survival differences. From our analysis, the FIGO stage and Histological sub-type are significant prognostic factors for survival.
Cervical Cancer is more common in Rural places of our country than in urban and western populations [7]. There have been variations in Cervical cancer based on location and treatment facilities available and that affects Health infrastructure Nationally and also globally. In-equality in Cervical Cancer survival is attributed due to various geographic, cultural, medical, genetic, and socioeconomic factors [8–10]. Few Western literatures showed there is no association between socioeconomic status and Cervical cancer survival [11]. But one South Indian study from Kerala showed socio-economic factors can affect Cervical cancer survival [12]. In a real-life scenario, one's socioeconomic status and factors can improve or decline during a timeline which makes us difficult in conducting a prospective study to find an association between socio-economic factors and survival. Also, these factors vary from place to place and cannot be uniform and standard which also makes the situation difficult to do a multi-centric study. What indirectly affect survival by delay in diagnosis and treatment are the cultural beliefs, sexual practices, health consciousness, nutrition, and access to health care [12]. These socio-economic factors also affect the percentage of dropout patients during treatment and loss of follow-up during surveillance.
Survival of cancer cervix has been reported way back in 1998 with an overall 5-year survival of about 51% [13]. In our study, the observed 5-year survival rates by stage of disease were 64.0%, 50.0%, 37%, and 17.5% for Stage I, Stage II, Stage III, and Stage IV, respectively. A globally released survival data- SURVCAN from different countries depicted India has poorer 5-year survival rates compared to other Asian countries [4, 14]. The survival rates also differ within India among various population registries (35.7%, 46.4%, 34.5%, and 59.6% in Barshi, Mumbai, Bhopal, and Chennai, respectively) [4]. Our survival analysis is compared to previous studies from India [6, 12, 13, 15–17]. The difference in survival can be attributed to various other factors like socioeconomic status, Education, Nutrition, patient's geography (rural or urban), treatment adherence and follow-up protocol, new advances in therapy, and other causes of non-cancerrelated deaths as confounding factors.
Even though multivariate analysis in our study doesn't show significant survival differences based on Education, Religion, and Marital status, it does show non-significant survival differences. These factors have been proven to affect Survival in cancer cervix in previous studies but most of them are similar to retrospective analysis like us [6, 12]. To make it a matter of concern, prospective randomized controlled trials are needed to find the exact role of these factors in affecting survival.
The incidence of cervical cancer has been decreasing in India for the past three decades [18]. But to decrease its impact on public health, information, education, and communication activities are needed for the community [18]. To improve survival in these rural population, awareness regarding screening and implementing screening programs, awareness regarding HPV vaccination, following good cultural and sexual practices, improving their socio-economic status, improving nutrition, and addressing all social factors helps in preventing the disease, early detection of cancer with curative treatment and proper follow up which in turn improves the overall survival rate.
Declarations
Conflict of interest The authors declare that there are NO conflicts of
interest. The authors whose names are listed immediately below certify
that they have NO affiliations with or involvement in any organization
or entity with any financial interest (such as honoraria; educational
grants; participation in speakers’ bureaus; membership, employment,
consultancies, stock ownership, or other equity interest; and expert
testimony or patent-licensing arrangements), or non-financial interest
(such as personal or professional relationships, affiliations, knowledge
or beliefs) in the subject matter or materials discussed in this manuscript.
