1Dr Rabindran, Consultant Neonatologist, Sunrise Superspeciality
Children’s Hospital, Hyderabad, 2Dr D Sharad Gedam, Professor
of Pediatrics, L N Medical college, Bhopal, MP, India
Address for
correspondence: Dr Rabindran , E-mail:
rabindranindia@yahoo.co.in
Abstract
Cervical cancer is the second most common cancer among women worldwide.
First priority to reduce deaths from cervical cancers is to implement
high quality, fully organised screening programmes without delay.
Knowledge about cervical cancer and Pap testing influences uptake of
cervical cancer screening services. Screening and treatment for
precancerous lesions is a more cost-effective intervention compared to
management of invasive cervical cancer. Human papillomavirus is the
etiologic agent of virtually all cases of cervical cancer worldwide.
All women 30 years and older should be routinely screened
&screening should continue until the age of 65 years. By
reducing the smear interval from 5 to 3 years in the age group <
50 years, the risk reduction for cervical cancer could be improved.
About 16% of the world′s total cases occur in india. At
current incidence rates, the annual burden of new cases in India is
projected to increase to 225,000 by 2025. However,the screening
coverage in india is low upto 2.6-5 percent.Of all the screening tests
available, the three main screening procedures commonly employed are
Papanicolaou smears (Pap smears), visual inspection with acetic acid
(VIA) and HPV testing . It has also been worked out that
‘once in a lifetime’ screening would result in
reduction of 20-30% of the lifetime risk of cervical cancer. Health
education is the most cost-effective approach in reducing the incidence
of cervical carcinoma in developing countries like India.
Key words:
Cervical cancer, Cervical cancer screening, Pap Screening
Cervical cancer is the second most common cancer among women worldwide
[1]. It is the leading cause of morbidity & mortality
in women [2]. About 80% of these cases & deaths occur
in developing countries [1].
Role
of Screening
Cervical cancer is a preventable disease because invasive cancer is
preceded by a long preinvasive stage, (upto 10 years) which may be
diagnosed and treated, & the lesion is available for
examination by simple methods [3]. Women who are not screened run a
higher risk of developing cervical cancer [4]. Early detection of
pre-cancerous lesions through cytological screening is the mainstay for
global control of the disease. In developed countries, the incidence
and mortality have markedly decreased after the introduction of
cytologic cervical cancer screening [5]. So our first priority to
reduce deaths from cervical cancers is to implement high quality, fully
organised screening programmes without further delay.
Barriers
for effective screening
The main barriers are insufficient contact with the physician, anxiety,
embarrassment , inappropriate beliefs, misconceptions , being
single& psychological unpleasantness associated with the
gynecological examination. Women belonging to low socio-economic status
& those living in rural locations lack adequate screening
facilities. Cervical cancer screening on an opportunistic basis has
resulted in low population coverage [6]. Women’s knowledge of
cervical cancer and Pap smear testing is very limited. About 65% of
subjects with invasive cervical cancer had never had a pap smear done
until diagnosis [7]. Knowledge about cervical cancer and Pap testing
influences uptake of cervical cancer screening services. Screening and
treatment for precancerous lesions is a more cost-effective
intervention compared to management of invasive cervical cancer. The
World Bank estimated that the cost of screening woman every 5 years was
USD100 per disability-adjusted life year (DALY) gained compared with
USD2600 per DALY for treatment/ palliative care of invasive cervical
cancer [8]. Seminars with experts in preventive care, guidelines
& pamphlets & giving patients a follow-up date for
their cervical smear results will increase effective screening.
HPV
& Cervical Cancer
Human papillomavirus (HPV) is the etiologic agent of virtually all
cases of cervical cancer worldwide [1]. When patients with disease are
compared for HPV infection with population-based controls, odds ratios
of 200 have been observed [9]. HPV 16 and 18 account for nearly
50–70% of cervical cancer cases worldwide [10]. HPV infection
is very common amongst sexually active young women with a prevalence
ranging between 20% to 46% [11]. The knowledge about HPV is deficit
worldwide. For HPV DNA testing to be useful for primary
cervical cancer screening, strategies need to be developed that avoid
identifying large numbers of women with transient infections ( less
common beyond 30 years) and focusing on identifying those
women with persistent infection. So restricting HPV screening to women
30 years of age and older would be cost- beneficial [12]. One way in
which HPV DNA testing could be utilised to screen large numbers of
women without access to speculum examinations is through the use of
self-collected vaginal samples. The sensitivity of HPV DNA
testing of a self-collected vaginal sample for CIN 2, 3 or cancer was
66% (95% CI: 52–78%), which was equivalent to that of the
conventional cervical smear [13].
Recommendations
for Screening
When to Start: All women 30 years and older should be
routinely screened [1]. Several recent reports indicate that the
incidence of cancer of the cervix in younger women is increasing [14].
Cytology may be relatively insensitive at detecting invasive tumours in
younger women , so the over-diagnosis, over-treatment and anxiety
generated by screening the under-25 age group outweighs the small
potential benefits. Among women aged 20 to 24 years to prevent 1
invasive cervical cancer, one would need to do between 12,500 and
40,000 additional screening tests & treat between 300 and 900
women [15]. However if the patient is HIV positive, screening should
begin at a younger age, or at the age of onset of sexual activity.
When to Stop: The
age-specific incidence of cervical carcinoma in a population that does
not undergo screening shows a peak at ages 45 to 50 years and a modest
decline at older age. Cruickshank et al., & Van
Wijngaarden& Duncan questioned the benefit of screening women
over the age of 50 years [16,17]. Enormous smears (420 000) are
required to prevent one death in over 50 years age group [17]. Moreover
less numerous cells and atrophic cells make the sensivity of the
Pap-smear test lower. The carcinomas in elderly women hardly
pass an in-situ stage. Symonds and Lamont however stated that women
aged over 50 years are at high risk of developing carcinoma cervix if
they have been inadequately screened, the survival after treatment
worsened with increasing age, and the preinvasive phase in older women
is very short [18]. In contrast to the former natural course, it now
appears that there are two age peaks in the invasive squamous cell
carcinoma incidence graph [19]. Current NHSCSP guidelines suggest that
screening should begin at the age of 25 & continue
until the age of 65 years.
Frequency of Screening
[20]
Age
Frequency
25
FIRST
VISIT
25-49
3
YEARLY
50-64
5
YEARLY
>65
those
who haven’t been screened before the age of 50 & those who had recent
abnormal tests
>65 those who haven’t been screened before the age of
50 & those who had recent abnormal tests
By reducing the smear interval from 5 to 3 years in this age group
< 50 years , the risk reduction for cervical cancer could be
improved from 30% to 41% , however the rise in cost may be
60–66% [20].
Methods of Cancer
Screening
Pap Smear
PROS : Best
Approach, Simple, Relatively Inexpensive, Reliable, Free of Risk ,
Highly Effective, Highly Specific, Most Cost-Effective, Highly
Valid& gives early Diagnosis at a Preinvasive Stage.
CONS: Inherent Subjectivity, Suboptimal Sensitivity , Limited
Reproducibility, Equivocal Results, Varying False Negative and False
Positive Rates , Varying Accuracy ( 30% - 90%), Screening insensitivity
for Adeno- &Adenosquamous Carcinomas , Technical Capabilities,
Requirement of trained personnel & Financial Resources , Lack
of coherence in Cytologic and Histopathologic Terminology, Fear,
Embarrassment, Pain, Inconvenience & Non-Optimal
Participation Rate.
Self-Sampling Device (SSD)
PROS: High
Acceptance. Can increase screening coverage for hard-to-reach
populations. CONS:
Inferior Cytological Quality compared with physician-collected samples
& cannot be evaluated by Conventional / Liquid-Based Cytology.
Liquid Based Cytology
PROS: Similar Sensitivity and Specificity as Conventional
Cytology, reduction in sample processing time . CONS: Lower
Sensitivity & Less Specificity.
Cervicography
PROS : Used
together with a pap smear, it can identify nearly 2.5 times the number
of women with dysplasia compared with the use of a pap smear alone,
more effective than cytology [21], High Sensitivity &
Acceptable specificity & more Sensitive in younger
women and in women not using progesterone-only contraception, in whom
the transformation zone is ectocervical. CONS: High
false positiverate .
Visual inspection of the
cervix with Lugol’s iodine
PROS : First
method of screening of the cervix introduced in the 1930s by Schiller
[22]. CONS: Very
Poor Specificity & Inherent Subjectivity.
Visual Inspection with
Acetic Acid ( DVI / Cervicoscopy/ Acetic Acid Test / Vinegar Test)
PROS :
Simple, Rapid, Inexpensive , Reliable, Reasonably Sensitive, detects
cancer early, Provides immediate results, has superior sensitivity than
Pap Smears, Cost-Effective, has high Negative Predictive Value (NPV)
which has important implications for national screening programmes. The
likelihood of a VIA-based screening programme for reducing
cervical cancer rates is being evaluated.
CONS:
Inherent subjectivity &Interobserver variability, low
specificities and positive predictive values (PPV), Low Sensitivity for
HPV, danger of overdiagnosis& over-treatment.
Hybrid Capture-II (HPV DNA Testing) Signal Amplification PROS :
Reliable, Accurate, Objective, greater sensitivity than cytology-based
screening, Superior PPV in detecting CIN compared to Cytology , useful
for detecting precursor lesions, Built-in quality control , Robust
& Reproducible, useful in older women in whom regression rates
are lower. Eliminates 80–90% of screened women from being
considered at risk for cervical cancer [23], has higher sensitivity ,
processing of results can be automated, more objective and requiring
less training of healthcare workers.Rapid HPV DNA tests provide results
within a few hours making same-day screening and treatment with
cryosurgery possible in selected women . Possibility of HPV testing as
a screening method for cervical cancer is being investigated.
CONS: Less
specific, high false negativity, may not be cost-effective if the ratio
of the prevalence of HPVinfections to the prevalence of CIN is high.
Colposcopy:
Examines cervix in greater detail (types of vessels found within
acetowhite lesions, quality of the margins, surface configuration,
contour & colour of the lesions)
p16INK4a:Indirect marker of persisting HR-HPV infection and malignant
degeneration of cervical cells. P16ink4a immunocytochemistry has a
significantly better specificity for high-grade CIN than HPV with
comparable sensitivity.
E6/E7 viral
mRNA : Used to risk-stratify.
Cervical Cancer:
Indian Perspective
Disease Burden In India:
Cervical cancer is the most common cancer among Indian women [24].
About 16% of the world′s total cases occur in india [25]. It
is estimated that approximately 100,000 indian women develop cervical
cancer each year [26]. At current incidence rates, the annual burden of
new cases in India is projected to increase to 225,000 by 2025.
Cervical cancer will occur in approximately 1 in 53 Indian women during
their lifetime compared with 1 in 100 women in more developed regions
of the world [27]. Between 1980 and 2010, little progress was made in
reducing cervical cancer mortality in India: 37 women died for every
100 new cases of cervical cancer in 1980 compared with 32 for every 100
new cases in 2010 [80 27]. High mortality rates are largely the result
of nearly 70% of cervical cancer cases in India being diagnosed at an
advanced stage (stage III or IV) [28].
HPV and Cervical Cancer
In India: In india also, HPV is the leading cause and is
associated with 90% of cases [29]. Approximately 70% of cervical
cancers in India are caused by HPV types 16 and 18, which are targeted
by the vaccine [30]. HPV vaccine awareness, access, and use are very
low in india .
Barriers of Effective
Screening In India: The screening coveragein in india is
low upto 2.6-5 percent [31]. Availability of Pap testing is very
limited, and there is hardly any infrastructure for performance of
colposcopy or management of cervical precancerous lesions. There is a
serious lack of awareness not only in the general population but also
in the medical fraternity and policy–makers in India&
few large-scale screening programs exist in India.
Role of Cervical
Screening In India: From a health policy perspective, the
screening system will save the Indian government millions of rupees
each year. While it costs about 2,000 rupees to treat a known case of
HPV, it can cost as much as 500,000 rupees to treat a woman with an
active case of cervical cancer and potentially cost her life. An
HPV-based test would probably be best because of its sensitivity. With
38% of cases occurring among women of reproductive age (15–49
years), the adverse social and economic impact of cervical cancer on
families and communities is considerable [27].
Screening Procedures In
India: of all the screening tests available, the three
main cervical cancer screening procedures commonly employed in India
arePapanicolaou smears (Pap smears), visual inspection with acetic acid
(VIA) and HPV testing.With the limited available resources
for cytology the Papanicolaou smear test could not be used as a public
health strategy for cervical cancer in India. Although cytology based
screening program using Papsmears have been found to be effective in
developed countries, alternative screening methods which can be more
effective in the settings with low resources is using either VIA or
VILI.HPV testing is the most objective and reproducible of all cervical
screening tests and is also less demanding in terms of training and
quality assurance.The HPV test costs around Rs.1250 per test in private
medical centres in India. A simple, affordable, and accurate HPV test
(care HPV test, Qiagen) that provides results within 3 hours was
evaluated in China. The careHPV test will be a boon to developing
countries like India.
Frequency of Screening
for India: It has also been worked out in the Indian
situation that ‘once in a lifetime’ screening would
result in a reduction of 20-30% of the lifetime risk of cervical cancer
[32].
Strategies To Promote
Cervical Screening In India: The strategies include
Mobilization efforts led by local health workers, Involvement of
community leaders, Use of advertising campaigns through print and other
media, Education of women, Recruitment through home visits by known
health care workers, Provision of screening appointments and
informational cards, Provision of screening & treatment
services at locations close to the community by female health care
providers & Provision of transportation to referral clinic for
diagnostic and treatment services.
Conclusion
There is no doubt that the control of cancer of the cervix is an
important issue for the health planners. Screening practices can
preferentially be directed to the target population for optimal
utilization of resources. Health education is the most cost-effective
approach in reducing the incidence of cervical carcinoma in developing
countries like India. Our conclusion and recommendations are that
heightened public awareness of cervical cancer prevention, focusing on
screening will lead to improved survival and a better quality of life.
Funding:
Nil, Conflict of
interest: None initiated. Permission from IRB:
Yes
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How to cite this article?
Rabindran, Gedam DS. Cervical cancer screening: current perspective.
Obg Rev: J obstet Gynecol 2015;1(1):3-8. doi: 10.17511/jobg.2015.i1.01.