Evaluating the Performance of Hybrid Capture 2 Test as a Primary Screening Test from Studies Conducted in Low and Middle-Income Country Settings- Special Focus India.

Kavita Anand,Gauravi Mishra,Sharmila Pimple,Atanu Bhattacharjee,Surendra Shastri

doi:10.31557/apjcp.2021.22.8.2709

Abstract

Among the screening tests for cervical cancer, advantages of screening with second generation molecular Hybrid Capture 2 (HC2) test is the high sensitivity and negative predictive value that makes it easy to implement as a cervical cancer screening policy necessitating less screening rounds. High income countries are now implementing HC2 test in their national cervical cancer screening program. Since the acceptance of any screening test depends on the sensitivity of the test, the current study was carried out to evaluate the sensitivity of HC2 test reported from Low- and Middle-income countries (LMIC) which share major burden of cervical cancer globally and to establish if HC2 test could be used as a primary screening test in India. Materials and methods:The population based cross sectional studies from LMICs which evaluated HC2 test as a primary screening modality to diagnose Cervical intraepithelial neoplasm grade 2 and above (CIN2+) lesions were included. Results:A total of 18 studies from LMIC involving 1,13,086 women were reviewed for sensitivity of HC2 as a primary screening test. The overall average sensitivity and specificity to diagnose CIN2+ lesions were 79.84% (95% CI-71.01,86.73) and 85.63% (95% CI- 84.37,86.92) respectively. India demonstrated an average sensitivity and specificity of 65% (95% CI 57,77) and 93% (95% CI- 92,94) respectively. Conclusion:Results from LMIC demonstrate a comparably low sensitivity of HC2 test to diagnose CIN2+ lesions as compared to that reported from High income countries. Sensitivity of HC2 was substantially low for India. The current study discusses issues of HC2 assay and the role of untreated Reproductive tract infections as probable causes for low sensitivity of the test. This needs further research in an attempt to improve the sensitivity of the test in an era of self-sampling and low-cost HPV test on horizon to improve the coverage for cervical cancer.

Highlights

The epidemiological studies have demonstrated the causal role of persistent oncogenic Human papillomavirus (HPV) infection as a main cause for cervical cancer (Walboomers et al, 1999; Bosch et al, 2002; IARC working group., 2007)
Since the acceptance of any screening test depends on the sensitivity of the test, the current study was carried out to evaluate the sensitivity of Hybrid Capture 2 (HC2) test reported from Low- and Middle-income countries (LMIC) which share major burden of cervical cancer globally and to establish if HC2 test could be used as a primary screening test in India
Data sources and searches This paper is based on information gathered from published peer-reviewed articles on cervical cancer screening in PubMed data base from year 2000 to 2019 since majority of articles on molecular HPV testing were published after year 2000. The keywords and their corresponding MeSH term used to build up search strategy were ‘cervical cancer screening’ OR ‘cervical intraepithelial neoplasm’ OR ‘cervical dysplasia’ AND ‘human Papillomavirus’ OR ‘HPV test’ OR ‘HC2 test’ NOT ‘HPV vaccination’ NOT ‘HPV self-sampling’ We examined bibliographies of relevant articles to identify additional references

Summary

Introduction

The epidemiological studies have demonstrated the causal role of persistent oncogenic Human papillomavirus (HPV) infection as a main cause for cervical cancer (Walboomers et al, 1999; Bosch et al, 2002; IARC working group., 2007). The cytology-based screening demonstrated significant decrease in cervical cancer mortality rates for developed countries (High income countries) but similar results were not evident for Low- and middle-income countries (LMICs). The cytology-based screening has limitation in terms of sampling technique, transportation issues, interpretation skills of laboratory personnel (Lazcano-Ponce et al, 1999; WHO, 2006), and short screening intervals needed due to low sensitivity of the test reported (Aggarwal et al, 2010). There are encouraging results from well conducted population-based trials from LMICs like India (Sankaranarayanan et al, 2009) and Mexico (Flores et al, 2003) demonstrating that, a simple and reliable molecular HC2 test which is available even in low-income countries has a potential to be accepted as primary screening tool in the near future. Since the potential of any screening test to be adopted by a country depends on the sensitivity and specificity (test characteristics), the aim of current review was to appraise the test characteristics of HC2 as a primary cervical cancer screening test reported from LMICs, especially from Indian context

Materials and Methods

12 Latin America

Discussion