Introduction
Cancer of the cervix is a global health problem, especially in developing countries
like India where effective screening programs are lacking in planning, organization,
and implementation levels.
It is also the fourth most common cause of cancer death (266,000 deaths in 2012) in
women worldwide accounting for 7.5% of all female cancer deaths. Almost nine out of
10 (87%) of cervical cancer deaths occur in less developed countries, and more than
one-fifth of all new cases are diagnosed in India.[1] Organized population-based screening linked to treatment of the detected neoplasia
can lead to more than 70% reduction of disease-related mortality.[2] The mortality and morbidity burden poses a heavy economic burden on families.[3] Mortality due to cervical cancer is also an indicator of health inequities,[4] as 87% of all deaths due to cervical cancer are in developing, low- and middle-income
countries.[5]
Cervical cancer prevention programs include a 3-stage intervention: Screening by Pap
tests/cervical cytology, colposcopic evaluation of screen positives, and directed
biopsy of abnormal looking cervical tissue for diagnosis and excisional or ablative
treatment of cervical tissue in women diagnosed with precancerous/cancerous lesions.
The incidence of cervical cancer can be decreased by regular screening and treatment
of precancerous lesions. Although Pap smear is central to screening, it has some limitations,
most important being its limited sensitivity which is between 47% and 62% and the
subjective interpretation of the results.[6] Survival rates for cervical cancer can be further improved by establishing effective
cancer treatment programs. Cervical cancer is preceded by a long period of premalignant
disease with increasing morphological atypia and the potential for progression to
malignancy. On an average, cervical cancer takes at least a decade to develop.
The pattern of gynecological malignancies varies among nations and even within health
institution in the same country. Understanding the histopathological pattern of these
will help in the management of the patient. Therefore, the histopathological examination
of the biopsies of cervical lesions is the single best gold standard for the diagnosis
of the lesions of the cervix.[7] The aim of the following study is to study cases of cervical cancers. Ours being
a tertiary care center with high patient load can give a better picture of the current
scenario to give histomorphological spectrum and establish the clinicopathological
correlation of cervical cancers in Central India. On the basis of this, a detailed
histomorphological study of the neoplastic lesions of the cervix was taken up our
institution.
Materials and Methods
All the uterine cervical biopsies and hysterectomy specimens (for cervical lesions)
received in our institution were evaluated retrospectively from January 2014 to August
2015. After standard grossing and processing procedure, the tissues were examined
in hematoxyline and eosin stained slides and histopathological evaluation was done.
The findings were correlated with age, symptoms, gravida, parity and other relevant
clinical details wherever deemed necessary. The biostatical analysis was performed
using program IBM SPSS (Statistical Package for the Social Sciences), for quantitative
data student’s t-test was applied. P value was considered statistically significant
if P < 0.05, and highly statistically significant if P < 0.01.
Results
A total of 180 cases were of neoplasia cervix. Among all the neoplastic lesions, moderately
differentiated squamous cell carcinoma with 92 (51.11%) cases was the most common
histological type of carcinoma encountered in our study followed by Nonkeratinizing
Squamous Cell Carcinoma (NKSCC), Well-Differentiated Squamous Cell Carcinoma (WDSCC),
Poorly Differentiated Squamous Cell Carcinoma(PDSCC), Adenocarcinoma (AdenoCa), and
Adenosquamous carcinoma with 25.56% (46), 11.67% (21), 8.33% (15), 2.78% (5), and
0.56% (1) cases, respectively.
Thus, the majority of cases were of squamous cell carcinoma type, i.e., 96.6% (174
cases) followed by AdenoCa constituting only 2.8% (5 cases). Among 174 squamous cell
carcinoma cases, 128 (73.5%) cases were keratinizing and 46 (26.4%) cases constituted
nonkeratinizing type.
Regarding age distribution, the mean age for neoplastic lesion was 50.67 years with
a high standard deviation of 10.86. Age distribution according to histomorphological
diagnosis is shown in [Table 1].
Table 1
Age distribution for neoplastic lesion of cervix
|
Diagnosis
|
Total cases
|
Mean age
|
Minimum age
|
Maximum age
|
|
MDSCC – Moderately differentiated squamous cell carcinoma; NKSCC – nonkeratinizing
squamous cell carcinoma; WDSCC – Well-differentiated squamous cell carcinoma; PDSCC
– Poorly differentiated squamous cell carcinoma
|
|
MDSCC
|
92
|
50.6
|
30
|
75
|
|
NKSCC
|
46
|
51.0
|
30
|
70
|
|
WDSCC
|
21
|
50.4
|
26
|
66
|
|
PDSCC
|
15
|
52.1
|
30
|
70
|
|
Adenoca
|
5
|
45.8
|
40
|
60
|
|
Adenosquamous
|
1
|
45.0
|
45
|
45
|
Youngest patient was of 26 years age and oldest was 70 years. Mean age was not significantly
different for different histological subtypes of squamous cell carcinoma with majority
being postmenopausal. The youngest female case of carcinoma was nulligravida and had
received no vaccination for human papilloma virus (HPV), however, sexual history was
unreliable.
Clinical presentation of cervical lesions
The clinical presentation of women was varied. Majority of cases (50.01%) complained
of postmenopausal bleeding followed by abnormal spotting (26.67%) and lower abdominal
pain (7.78%). White discharge with abdominal pain constituted a mere 6.66% of cases
followed by growth (6.11%), postcoital bleeding (1.67%), and pyometra (1.11%).
Gravida
Average gravida of females in our study was found to be 3.78. Twenty-six (14.4%) cases
had 0–2, 113 (62.7%) had 3–4, whereas 42 (23.3%) cases were grand multipara (>5).
Staging of cervical cancers
According to the Federation of Gynecology and Obstetrics (FIGO) staging of patients
included in our study, most common presentation was in Stage IIB with 45.56% (82)
cases followed by Stage IIIB with 21.02% (37) cases and IIIB with 21.02% (29) cases.
As per the WHO, advanced cervical cancer means cancer that has grown into tissues
around the cervix, i.e., Stage IIB, or spread further. In the present study, 158 (87.8%)
women presented in advanced stage of cervical cancer. Cases amenable to early treatment
and better prognosis constituted only a handful (Stage IB), i.e., a mere 3.33%. While
cases presenting with distant metastasis and worst prognosis (Stage IV) were mainly
in older age group.
On the basis of FIGO staging with respect to different histological subtypes, 92.9%
of cases of keratinizing squamous cell carcinoma were in advanced stage compared to
73.9% in nonkeratinizing squamous cell carcinoma. All cases of adenocarcinoma presented
in advanced stage. On statistical analysis, keratinizing squamous cell carcinoma were
found to have poor prognosis compared to nonkeratinizing squamous cell carcinoma and
the difference was highly significant with P = 0.006 (P < 0.01). However, with respect to AdenoCa, results were insignificant.
Other factors
Majority of females had poor personnel hygiene habits. Only 4% used oral contraceptives,
a minority used barrier method while majority used no contraceptives and had tubal
sterilization after family completion.
None of the females had received any HPV vaccines in their lifetime. There was a nominal
level of awareness with regard to this vaccination and those few who were willing
perceived the cost to be high as per their financial affordability.
Majority of women in our study had menarche at 12–13 years of age and had first sexual
exposure before the age of 20 years. A majority of them also had their first conception
before reaching 20 years and almost all had completed their family by 30 years of
age. Breast feeding was nonexclusive.
Discussion
Cancers of cervix have a considerable burden on our health system as well as has social
and financial implications. We studied the histomorphological variations of cancer
cervix in our institute. Squamous cell carcinoma was the most common histological
type of cervical cancer as observed by Olu-Eddo et al.,[8] Okoye,[9] Abudu et al.,[10] Pathak et al.[11] and Ikechebelu et al.[12] with 92.3%, 84.2%, 93.6%, 92.56%, and 89.6% cases respectively which is similar
to our study with 96.67% of cases. Okoye [9] had slightly less proportion of cases probably because they included metastatic
carcinoma in their study group unlike other studies.
In USA, a study by Adegoke et al.[13] for trends in cervical cancers for 35 years revealed that overall incidence of squamous
cell cancer decreased annually between 1973 and 2007 by 8%, and the incidence of AdenoCa
increased by an average of 2.9% per year over the same period. This reversal of trend
is attributed to the fact that cervical screening programs consisting of mainly Papanicolaou
smear examination has better sensitivity and specificity for squamous lesions compared
to AdenoCa.
Adeniji [14] observed WDSCC (60.1%) as most common subtype whose study period was almost four
decade earlier than the present study. There is a clinical correlation between the
degree of differentiation of a tumor and its clinical behavior; well-differentiated
tumors tend to be less aggressive than poorly-differentiated ones; however, this is
not conclusively substantiated by studies yet.
Cancer of the cervix can develop in women of all ages. It usually develops in women
aged 35–55 years with the peak age for incidence varying with populations; for instance,
it is 30–40 years in UK and 35–39 years in Sweden (Cancer Research UK). In India,
the peak age for cervical cancer incidence is 45–54 years, which is similar to the
rest of South Asia.[15]
Among neoplastic lesions of cervix uteri, we made age parameter comparison with other
studies [Table 2].
Table 2
Comparison of age parameters with other studies
|
Studies (place)
|
Time period
|
Age range
|
Peak decade
|
Mean age+SD
|
|
SD – Standard deviation
|
|
Adeniji[14] (Nigeria, Africa)
|
1979-1997
|
23-85
|
5th
|
51.8
|
|
Olu-Eddo et al.
[8] (Benin, Africa)
|
1987-2006
|
15-90
|
5th
|
50.4+13.5
|
|
Okoye[9] (Nigeria, Africa)
|
2000-2009
|
18-99
|
5th
|
51.5+12.8
|
|
Jeebun et al.[16] (Mauritius, Africa)
|
2000-12
|
-
|
5th
|
50.6+10.6
|
|
Abudu et al.[10] (Olabisi, Africa)
|
2003-2004
|
31-70
|
4th
|
-
|
|
Pathak et al.[11] (Nepal)
|
2013
|
24-92
|
4th
|
42.5
|
|
Present study
|
2014-2015
|
22-75
|
4th
|
50.6+10.8
|
Thus, we observed that as the study period shifted to more recent times, detection
peak of cervical cancers shifted from the 5th to 4th decade. This is possibly due
to increased awareness among women regarding gynaecological problems as well as increased
per capita income and better health-care facilities.
Clinical presentation of females with carcinoma as observed by Ikechebelu et al.[12] i.e., abnormal vaginal bleeding (postmenopausal/postcoital/abnormal spotting) was
similar to present study.
With respect to cases with grand multipara, Ikechebelu et al.[12] observed majority in this category with mean gravida of 6.8 compared to 23.33% cases
in the present study. Ikechebelu et al.[12] observed 89.3% cases in Stage III and IV compared to 42.2% of cases in the present
study. This highlights the fact that cases presenting in late stages of carcinoma
has a welcome decreasing trend due to various reasons such as better health-care facilities,
accessibility, screening camps, increased awareness, and confirmatory histological
diagnosis as well as better and early treatment by surgeons.
In conclusion, although the clinical presentation were more or less similar, the peak
age presentation was a decade earlier than most of the studies (later half of the
4th decade versus 5th decade). Majority of cases were in Stage IIB (45.56%) followed closely by advanced
Stage (III and IV) with 38.8%.
We observed that women were reluctant in approaching health clinics for gynaecological
symptoms. Furthermore, none of the cases had HPV vaccination before the first sexual
encounter. Although awareness regarding the same is increasing, cost and social stigma
are the main deterrent factors for females in the current scenario.
Early screening of the disease through cytology has considerably reduced morbidity
and mortality from the disease in the developed world.[17] There is an urgent need for regular and effective cervical screening program in
developing countries. HPV vaccination should be included in universal immunization
program of India. Presently, due to the expensive HPV vaccine and limitations of cytology
based screening programs owing to infrastructure, equipment and workforce -death and
disability from this cancer are high in developing countries including India.[18]
Women being the main caretaker of children as well as an almost equal economical contributor
in current era, needs to be properly screened for malignancies and detecting cases
in the early stage of Cervical Intraepithelial Lesion will go a long way in reducing
morbidity and mortality. Although there are many national programs successfully running
for obstetrics cases, same is lacking for gynaecological problems.
The World Health Organization recommends that in low resource settings like ours,
every woman should be screened at least once in her lifetime at 40 years. Frequency
of screening should be increased to “once every 10 years” and then once every 5 years’
for women 35–55 years of age. The frequency could be increased based on resources.[19] More research in the present context is needed so that best practices for the prevention
and control of cervical cancer in Indian scenario can be developed and implemented.
Cervical cancer causes loss of productive life both due to early death as well as
prolonged disability. In addition, the high medical costs incurred by families due
to cervical cancer (especially since most cases in developing countries are diagnosed
at advanced stages when treatment is costly but prognosis poor), further impoverish
people.[20]
HPV infection and precancerous lesions go unnoticed and develop into full blown cancer
before women realise they need to go for medical help.[21] HPV is a sexually transmitted infection, making cervical cancer a chronic disease
with an infectious aetiology.[6] The main risk factor for the development of cervical cancer is HPV infection, DNA
of which has been found in almost all cases of invasive cervical cancer in a study
by Bosch and de Sanjosé[22] Atleast 50% of sexually active men and women get HPV once a lifetime.[23] Majority of females usually have self-resolving HPV infection which does not evolve
into cancer cervix, however around 10% develop persistent infections, and are at high
risk of developing cervical cancer.[24]
WHO recommends 9–13 year old girls who have not yet become sexually active as target
group for HPV vaccination.[25] Schools may be targeted for giving better reach and coverage for future vaccination
programs and will go a long way in reducing the burden of cervical lesions both nonneoplastic
and neoplastic if implemented properly. Where school enrolment of girls is high, school-based
vaccination is a possibility; however, different approaches are needed to reach girls
not in school and who may be particularly vulnerable (e.g., street children, migrants).
Attracting young girls to repeatedly come to health facilities and outreach sessions
is likely to take special efforts.[25]
National educational campaigns for vaccine introduction should be used to increase
community awareness about cervical cancer and its prevention. Designed messages are
essential to educate communities, parents, teachers, adolescents about the HPV infection,
vaccine and cervical cancer. Sex education is as important as vaccination and use
of barrier methods goes a long way in protecting against all veneral diseases. Programs
can be quickly undermined by misinformation if the reasons for targeting girls only
are not fully and sensitively communicated. Educating men about HPV vaccines and cervical
cancer is particularly important in a patriarchal society like ours. Involving mothers
of young teenage girls and educating girls regarding advantage of screening procedures
is another communication opportunity.[25]
In finance constrained setting like ours, cost of vaccine as well as operational cost
for delivery also needs to be taken into consideration during planning process itself
and will be a critical step in the decision-making process.
Due to difficulties of access and affordability, compliance and follow-up of treatment
is much worse for women of low socioeconomic strata, leading to further morbidity
and mortality from the disease. Despite the fact that early detection and treatment
are one of the priorities of National Cancer Control Programme in India, yet there
is no organized Cervical Cancer Screening Program in our country and same should be
advocated and implemented at the earliest. We hope and recommend that this study will
lay the foundation for policy makers to effectively prevent and control cervical lesions,
especially cancers in the present and future scenario.
Conclusion
Cervical cancers pose a substantial burden on our social and health-care system. Although
surgery and radiotherapy remains the mainstay of treatment, nothing can replace prevention
and early detection of neoplastic cervical lesions. There is an urgent need for inclusion
of HPV vaccination programs in Universal Immunization Program of India. Large scale
screening programs for target populations should be organized to reduce the long term
morbidity, mortality and socioeconomic burden related with cervical lesions. Furthermore,
increasing literacy rate, personnel hygiene, socioeconomic strata, and use of contraceptive
measures to reduce parity will be highly instrumental in tackling the current and
future burden of cervical cancers. Histomorphology remains the mainstay of diagnosis
of cervical cancers. In low compliance settings such as ours, colposcopy-guided biopsy
is the preferred course of management, especially in elderly females to be definite
so as to rule out or diagnose neoplasia. National level cervical cancer program is
immediate need of the hour and should include HPV vaccine, awareness and screening
programs as well as treatment assistance for low socioeconomic strata. We recommend
effective programs to be included in government health schemes to prevent and control
cervical cancers in future as well as improve the present scenario.
