Keywords
cervical cancer screening - HPV test - HPV self-sampling - art-based strategy - low-resource
settings
Introduction
India reports a high burden of cervical cancer.[1]
[2] The factors contributing to a high burden of disease are the lack of health care
infrastructure and access to available facilities. Among social determinants, low
literacy level, lack of awareness of cervical cancer symptoms and lack of priority
of women's health issues are some of the contributing factors.[3] These factors together have a potential to lead to a global disparity in terms of
population coverage for cervical cancer screening in India. A population-based survey
conducted across 57 countries reported cervical cancer screening coverage of 19% on
an average in developing countries compared with 63% in developed countries. The author
commented that older and poor women, who are at the highest risk of developing cervical
cancer, are least likely to be screened.[4]
Currently, India does not have an organized screening program. Although visual inspection
with acetic acid (VIA) is a recommended screening test, it is challenging to sustain
and scale up the program due to repeated training, quality control, and screening
rounds needed.[5] To avail VIA test, women need to visit health care facilities with trained health
personnel to perform the test. This scenario represents programmatic barriers for
screening in terms of accessibility and human resources. Currently, there is sufficient
evidence from epidemiological studies about the causal role of persistent oncogenic
human papillomavirus (HPV) infection and cervical cancer.[6]
[7] The direct detection of HPV in cervical specimens by a molecular test can offer
an alternative for cytology/VIA-based screening. Among the various emerging HPV molecular
tests, the hybrid capture-2 test (HC2) has been extensively evaluated in various health
care settings.[8]
[9] The test identifies women at the risk of developing cervical cancer, needing a close
follow-up.[10]
[11] The advantages of HPV-DNA molecular test are high sensitivity (reported from developing
countries), longer screening intervals if tested negative, the potential of self-collection,
reproducibility, and standardization of the test.[10]
[12]
[13] HPV self-sampling (HPV-SS) is posed to be a viable option to increase the uptake
of cervical cancer screening among women. At the national level implementation strategy,
the test has the additional advantage of reducing the human resources in terms of
empowering the women to undertake their own test.[14]
Among all the above factors, the current study mainly explores the potential of acceptance
of HPV-SS as a preferred screening method by Indian women. India is a country with
diversities. Promoting HPV-SS shall need effective information, education, and communication
materials (IEC) in generating awareness toward screening and performing the HPV-SS
test with confidence among the beneficiaries. This is crucial in settings where illiteracy
is a key barrier in undertaking cervical cancer screening tests.
The current paper discusses interim results of the main study in terms of acceptability
of self-sampling as a screening modality to increase the coverage for cervical cancer
screening, the impact of communication modalities of IEC materials (the health education
arm versus pamphlet arm) to increase the uptake of HPV-SS, and quality of HPV-SS measured
in terms of agreement rates between the HPV-SS and primary health care worker collected
HPV samples (HPV-PHW) among women in the slum settings in Mumbai, Maharashtra.
Quality of HPV-SS measured in terms of agreement rates between the self-sampling and
HPV-PHW among women in the slum setting was considered as a primary objective of the
study.
Materials and Methods
Inclusion Criteria
Inclusion criteria were sexually active non-pregnant women in the age group of 30
to 55 years with no previous history of cervical cancer.
Exclusion Criteria
Exclusion criteria were women not sexually active, who underwent total hysterectomy,
with prior treatment history for cervical cancer, and pregnant or postpartum 6 months.
Study Design
The main study was a cross-sectional study proposed to be implemented across three
communities: namely (1) urban slum area, (2) urban non-slum area, and (3) rural area
([Fig. 1]). Herein, we tried to understand if HPV-SS would be similarly or preferentially
accepted by specific groups. For each setting, three clusters were identified and
one of the clusters under each setting was selected by a lottery method for implementation.
The current study presents the results of urban slum community settings collected
during the study period of 12th April 2021 to 24th June 2021.
Fig. 1 Demonstrates the detailed methodology of study. *Cervical intraepithelial neoplasia.
As per our hypothesis, the modality of communication may influence cervical cancer
screening uptake and quality of self-sampling. To address this, the current study
was designed with two interventional arms—(1) health education arm and (2) pamphlet
arm. Each selected cluster was then demarcated for two interventions using geographical
landmarks. In the health education arm, primary awareness for cervical cancer (risk
factors, types of screening tests, and advantage of early diagnosis and prevention)
and steps demonstrating the method to collect HPV-SS was explained in the local language
using flip charts/posters by medical social workers (MSW). In the pamphlet arm, art-based
strategy pamphlets with self-explanatory pictorial illustrations demonstrating the
steps of the procedure of collecting HPV-SS were distributed by MSW.
Methodology
As per the literature, the prevalence of HPV in self-sample is assumed to be 7 to
10%. To get a concordance rate of 80%, at 95% confidence interval (CI) and power of
80%, estimated sample size comprised 1,600 women (500 under urban slum settings, 500
under urban non-slum settings, and 600 under rural settings) to undergo HPV testing
by both the methods for the main study.
Under the current study, a total of 500 women, 250 women in the health education arm
and 250 women in the pamphlet arm, were enrolled. After the detailed mapping of the
area, door-to-door survey was conducted by trained MSWs to register eligible women
and invite them to participate in the study. Eligible women were enrolled following
informed consent, and the study questionnaires were completed.
After the awareness session as per the arm assigned, HPV-SS kits were distributed
to women in both groups. Used/unused kits were collected either on the same day or
within 72 hours by the MSWs. All women enrolled in the study were invited for HPV-PHW
samples. The women who tested positive on either HPV tests were referred to the tertiary
care center for further diagnostic workup.
The MSWs and the PHWs recruited under this trial received intensive training on delivering
the standard health education on cervical cancer for 4 weeks. MSWs were additionally
trained for conducting survey, mapping, and HPV-SS test. PHWs received hands-on training
in collecting HPV samples using the HC2 test for an additional period of 4 weeks in
the institutional department as per the standard operating protocols (SOPs). The audit
for quality control was planned every month.
Screen Positivity Criteria for the HC2 Test
Screen Positivity Criteria for the HC2 Test
To diagnose HPV infection, samples were processed by the HC2 test which has probes
for 13 recognized oncogenic HPV types. The relative light unit/cut-off ratio ≥1, corresponding
to 5,000 or more copies of virus in a sample, is considered a positive test. The transportation
of the samples from the field to institute was as per the SOPs of the Institutional
Department of Microbiology.[8]
[9]
Statistical Analysis
The quantitative data related to the study's objective were captured and analyzed
using IBM SPSS statistics for windows, version 25.0 (IBM Corp, Armok, NY, United States).
For the current paper, agreement between the HPV-SS and HPV-PHW samples using the
molecular HPV test was analyzed using Kappa statistics for the probability of chance
along with 95% CI.
Ethics
The female participants were enrolled only after informed written consent was obtained.
The study was conducted in accordance with the Declaration of Helsinki and Good Clinical
Practices as defined by the International Conference on Harmonization. The study received
clearance of the Tata Memorial Hospital Institutional Review Board on 2nd March 2017,
Project No- 1686.
Results
The overall acceptance of HPV-SS was 97% (485) in the target population ([Table 1]). The acceptance of HPV-SS was 100% (250) in the health education arm and 94% (235)
in the pamphlet arm for all those receiving the instructions in both formats. The
agreement between the HPV-PHW sample and the HPV-SS was demonstrated to be 94.69%
(232) and 95.61% (196) in the health education arm and pamphlet arm, respectively.
Overall, the agreement rate was 95.11% (428). The kappa value demonstrated moderate
agreement between the two samples readings by the HC2 test, k = 0.55 (95% CI = 0.34–0.77), p < 0.001.
Table 1
Acceptability and agreements between HPV self-sampling and health worker collected
HPV samples between the health education arm and pamphlet education arm as modalities
of communications
|
Variable
|
Health education arm
n = 250
|
Pamphlet education arm n = 250
|
Total n = 500
|
|
1. a. Acceptance of self-sampling
|
|
Acceptance of self-sampling n(%)
|
250 (100%)
|
235 (94%)
|
485 (97%)
|
|
1. b. Agreements between samples
|
|
Health worker collected sample
|
Health worker collected sample
|
Health worker collected sample
|
|
HPV test result
|
+ ve
|
− ve
|
Total
|
+ve
|
− ve
|
Total
|
+ ve
|
− ve
|
Total
|
|
Women self- collected sample
|
+ ve
|
9
|
7
|
16
|
7
|
4
|
11
|
16
|
11
|
27
|
|
− ve
|
6
|
223
|
229
|
5
|
189
|
194
|
11
|
412
|
423
|
|
Total
|
15
|
230
|
245[a]
|
12
|
193
|
205[a]
|
27
|
423
|
450[a]
|
|
Agreement
|
232 (94.69%)
|
196 (95.61%)
|
428 (95.11%)
|
|
Kappa (95% CI)
|
0.55 (0.34–0.77)
|
0.58 (0.34–0.83)
|
0.57 (0.40–0.73)
|
Abbreviations: HPV, human papilloma virus; −ve, negative for HPV in cervical sample; + ve,
positive for HPV in cervical sample.
a Women gave self-collected sample and health worker sample was also collected.
Discussion
In India, cervical cancer is a vivid indicator of health inequality within the country
with the burden of disease reported high among rural and low-income areas.[15] Hence, all efforts should be made to cover this hard-to-reach population to reduce
the incidence and mortality rates for the country. The current article reports interim
data on acceptability and quality of HPV-SS among women in urban slum settings using
a camp-based approach. Only slum women were selected for the current paper as they
face challenges such as non-availability of washrooms in the household and lack of
privacy for collecting self-samples.
This setting was high risk for HPV infections in terms of low economy, risky behavior,
sharing common toilets, and low vaginal hygiene. The women enrolled in the study were
in the median age group of 38 years which is a recognized age for the persistence
of oncogenic HPV infection. A single round of screening in this age group has the
advantage of prevention and downstaging of the disease.[14]
[15] The study overall demonstrated high acceptability (97%) of HPV-SS among this group
of women ([Table 1]).
Moreover, beyond acceptance of the test, it is crucial that women perform the test
with precision. There are numerous studies that have reported comparable performance
of self-sampling to clinician collected samples.[16]
[17] To our knowledge, this is the first study that compares the performance between
the self-collected and trained PHWs collected HPV samples. Our study also demonstrates
comparable agreements between HPV-SS and HPV-PHW samples. Understanding that the majority
of Indian population resides in rural areas with illiteracy and social stigmatization[18] being a major barrier in taking the test, it becomes important to understand, develop,
and evaluate appropriate IEC materials to raise awareness toward cervical cancer and
the screening test to be implemented. The educative materials also need to be effective
in de-stigmatizing and facilitating the undertaking of screening. Prior knowledge
of the screening test helps women to do so confidently. Currently, resources are needed
for one-to-one counseling for women before preparing them to undertake HPV-SS.[16]
[17]
[19] This strategy may not be feasible in human-resource-constrained countries like India.
The art-based health promotion strategies have been proven effective in facilitating
and mobilizing women among diverse settings. These strategies are warranted in low-resource
settings.[19]
[20] The strength of our study design is the use of two modalities of communication in
two groups, which shall help us understand the effective communication modality. The
current study demonstrates an equally good acceptance of HPV-SS by women in the pamphlet
arm comparable to the health education arm ([Table 1]). Recruiting and training MSWs and PHWs as project staff for implementation shall
help us understand the time needed for capacity building and quality of deliverables
with the goal of transferrable skills. This is an attempt to understand the feasibility
of integrating HPV-SS in public health systems.
Conclusion
The initial findings of the study support the acceptability of HPV-SS as a primary
screening test in the targeted population. In resources constraint settings, the current
finding demonstrates the potential of art-based strategy as a modality in facilitating
HPV-SS among women. The study also supports the feasibility of rapidly training para-medical
staff in implementing the test at ground levels. These findings are encouraging toward
building a sustainable and operational cervical cancer screening model for the country.
