Cervical cancer is a major public health problem in many developing countries and
the
absolute burden will increase in future if effective prevention measures are not undertaken.
The global estimates for cervical cancer burden in the world around the year 2008
indicated
that there were 5,30,232 new cases, 2,75,008 deaths, with four-fifths of the estimated
global burden occurring in the low- and middle-income countries (LMICs) of South and
South
East Asia, sub-Saharan Africa, and South and Central America1. In this issue Singla
and colleagues2
report the results of a ‘see-and-treat’ approach combining visual screening
with acetic acid (VIA)/Lugol's iodine (VILI), colposcopy and loop electrosurgical
excision procedure (LEEP) in the context of a cervical cancer screening study in New
Delhi,
India.
‘See-and-treat’ electrosurgical loop excision of the cervical transformation
zone is an excisional surgical procedure that enables simultaneous histologic diagnosis
and
treatment of cervical precancerous lesions, thus eliminating the need for a cervical
punch
biopsy and an additional visit. It involves two visits instead of the three visits
[first a
screening visit, a second visit for colposcopy and directed biopsy and the third visit
for
treatment of confirmed cervical intraepithelial neoplasia (CIN) cases] needed using
Pap
smear screening; however, it may be carried out in a single visit following VIA/VILI
screening as the results of screening are immediately available facilitating immediate
colposcopy and treatment with LEEP or cryotherapy.
The above approach should not be confused with a single visit
‘screen-and-treat’ when screen-positive women, without evidence of invasive
cancer, are treated with cryotherapy or cold coagulation, without triaging procedures
such
as colposcopy and biopsy; ‘screen-and-treat’ eliminates investigations to
confirm a diagnosis prior to treatment and minimises loss to follow up, delay in treatment
and missed disease3. A major concern with
‘screen-and-treat’ cervical cancer prevention strategies is that a large
number of women without precursor lesions will undergo cryotherapy/cold coagulation,
although there are no data to suggest that overtreatment is harmful. On the other
hand, it
may provide some marginal benefit by protecting women against future HPV infection
and by
reducing cervical ectopy and targeting the transformation zone (TZ) where cervical
neoplasia
occur. Current evidence suggests that screen-and-treat interventions are safe, well
accepted
by women and effective in preventing cervical neoplasia4
5. Currently, Thailand is implementing a
large ‘screen-and-treat’ programme with VIA and cryotherapy in 20 provinces
and more than a million women have been screened with this approach6.
Singla and colleagues2 demonstrated the clinical
utility, safety, and acceptability of “see-and-treat” approach using
cross-sectional data in the Indian context and showed that the overtreatment associated
with
this approach was minimal, though the study sample size was rather small.
‘See-and-treat’ LEEP has already been used for treatment of 1141 women during
2000-2004 screened with VIA or cytology or HPV testing in the context of a population-based
large randomized screening trial in Osmanabad district in Maharashtra in India7 to
maximize adherence to treatment and to minimise
loss-to-follow up by reducing the number of visits, which has been the objective of
the
present study in New Delhi. In this study, all the women had satisfactory colposcopy
and had
a prior punch biopsy before LEEP; on the other hand, most women involved in the Osmanabad
study had unsatisfactory colposcopy (51%) and had no prior punch biopsy (71%).
The overtreatment rate in New Delhi study was 12.5 per cent where as it was 45 per
cent in
the Osmanabad study7, and these differences are
likely due to the difference in the sources (hospital vs. general population) of screened
women and sample sizes between the studies.
As discussed by Singla and colleagues2,
“see-and-treat” LEEP has been used in hospital-based health care settings in
developed countries, in Latin American countries and China, involving women with
cytologically high-grade squamous intraepithelial neoplasia (HSIL) referred to colposcopy
clinics for further assessment and has been accepted as a useful option for the management
of women with cytological HSIL8–14. The overtreatment was significantly higher when
women with low-grade cytological abnormalities were included in
‘see-and-treat’ LEEP assessments14.
In developed countries, selective use of ‘see-and-treat’ LEEP is practiced by
experienced colposcopists who are able to reliably differentiate low-grade from high-grade
disease by means of colposcopy; it is resorted to mostly if cytologic and colposcopic
findings unequivocally indicate high-grade cervical intraepithelial neoplasia. On
the other
hand, the Indian studies2
7 involved screen-positive women with all grades of precancerous lesions
suspected at colposcopy. Thus, it is not surprising to see a high level of overtreatment
reported in the Indian studies as compared to studies in developed countries.
Another novel ‘see-and-treat’ approach combined VIA, colposcopy and
cryotherapy after directed punch biopsies in one or two visits in the treatment of
women
with colposcopic features of both high- and low-grade lesions in Osmanabad and Dindigul
districts in India in the context of population-based randomized controlled screening
trials15
16. These were large studies involving a total of 3581 women with colposcopically
suspected lesions. Punch biopsies directed just prior to cryotherapy allowed the
documentation of the histological nature of the lesions a posteriori after
the treatment, and revealed that 40.3 per cent women did not have histologically confirmed
CIN, indicating the level of overtreatment. ‘See-and-treat’ LEEP or
cryotherapy were associated with a higher level of overtreatment, when women with
features
of suspected low-grade lesions were included, than studies involving those with suspected
high-grade precancerous lesions7
15
16. However,
as pointed out by Singla and colleagues, ‘see-and-treat’ with LEEP needs to be
performed by doctors2
7 as a higher skill level is needed for LEEP, whereas
‘see-and-treat’ with cryotherapy can effectively be carried out by nurses as
shown in the southern Indian study16.
Although it has been proposed that ‘see-and-treat’ LEEP may be considered as
the work horse for the management of women with precancerous lesions in developing
countries17, this is feasible only in selected
instances. A more pragmatic approach is ‘screen-and-treat’ cryotherapy, which
is much more feasible and affordable, particularly when a large volume of screen positive
women with CIN has to be managed15
16.
It is worthwhile to consider the current status of cervical cancer in India, the country
presenting the largest burden of disease in the world. One of every five cervical
cancer
patients in the world is an Indian woman1. In spite
of this heavy burden and the important demonstration of feasible and cost-effective
screening and treatment approaches for cervical cancer prevention in a number of
well-conducted research studies in India, there has been very little scale-up of cervical
cancer screening services in the country.
Despite the depressing statistics on cervical cancer, there is no government sponsored
public health policy on prevention by either screening or vaccination or both in India.
This
large burden has not yet sufficiently seized the attention of public health authorities
and
there has been very little progress in publicly funded cervix cancer prevention initiatives.
That significant progress could be made is clear from encouraging initiatives taken
in
countries such as Thailand, Bangladesh, Brazil, Argentina, and Mexico among others18–22.
The situation is paradoxical given not only the large burden of disease but also that
India
has been responsible for some of the world-leading research demonstrating feasible
and
cost-effective approaches for cervical cancer screening and prevention in low- and
medium-resource countries23–32. Randomized trials in India have shown a significant
reduction in cervical cancer mortality following single round of screening with HPV
testing23 or VIA screening24. Studies from India have shown the safety, feasibility
and efficacy
of out-patient treatments for CIN2
7
15
16
25. These
data from India have catalyzed both implementation and reorganization of national
screening
programmes in countries such as Argentina, Bangladesh, Morocco and Mexico among others,
but
little up-scaling of screening has happened in most States of India other than Gujarat,
Maharashtra, Kerala, Tamil Nadu, Sikkim and West Bengal33. Bangladesh, for example,
has established a VIA screening programme which uses
both ‘screen-and-treat’ LEEP or cryotherapy for managing lesions, taking leads
from the Indian studies19. Mexico is the first
country in the world to establish primary testing with HPV followed by Pap smear triage
as
their national policy, based on their own research studies and the outcome of research
studies in India, Canada and Europe. They have already established a large network
of high
technology laboratories and have screened several million women with HPV tests. In
Brazil
more than 95 per cent of the municipalities provide Pap smear services and around
12 million
smears are taken annually and the Brazilian Government has recently allocated an additional
2.4 billion USD for cervix and breast cancer screening over the next four years34.
A further challenge to reducing the burden of cervical cancer in Indian women is the
misinformation about the safety and efficacy of HPV vaccination as a control strategy,
resulting in costly delays in resolving the controversies35–37. Meanwhile, neighbouring
Bhutan introduced HPV vaccination as part of the national immunization programme.
Malaysia,
Panama, Mexico and Argentina are also implementing HPV vaccination of girls aged 10-13
yr
either nationally or in selected provinces with high risk of disease. The time has
arrived
for India to take full advantage of the seminal research conducted on cervical cancer
prevention in the country in order to tackle its own high burden of this disease and
to
prevent it. Cervical cancer predominantly affects socio-economically disadvantaged
women;
offering opportunities to reduce the suffering associated with this eminently preventable
cancer is an ethical imperative that should go hand-in-hand with the remarkable economic
progress the country is now achieving.