An ensemble feature ranking framework for the assessment of the efficacy of cervical cancer detection tests and human papillomavirus genotypes in the detection of high-grade cervical intraepithelial neoplasia and cervical carcinoma

In most cases, cervical cancer (CxCa) develops as a result of underestimated abnormalities present in cytology via the test Papanicolaou (Pap test). Although it is the sole test that has proved its value for cancer prevention, Pap test is prone to human errors as it is performed via the microscope and requires skilled personnel. Consequently, molecular techniques have emerged in the recent years, aiming to replace Pap test or support the diagnosis as ancillary tests. These include DNA micro-arrays identifying Human Papillomavirus (HPV) subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. These techniques are either highly sensitive or highly specific, but not both at the same time, thus no perfect method is available today. Moreover, most of the published studies compare two tests against each other, which, however, are using different population study groups, therefore it is questionable if the results can be used to perform a direct comparison between the available tests. In this paper, we adopt a sophisticated approach to assess the value of several well-known and widely applied CxCa tests in detecting high-grade cervical intraepithelial neoplasia and CxCa (CIN2+), by employing an Ensemble Feature Ranking framework. Applying the proposed framework we managed to directly compare and rank the studied CxCa tests and several HPV genotypes according to their efficacy in detecting CIN2+ lesions. The results suggest that HPV mRNA tests perform better than HPV DNA testing for the triage of abnormal Pap tests. Such findings may guide cytopathologists in a step by step basis to decide which tests to perform following an abnormal Pap test, in order to decrease uncertainty, improve accuracy and reduce time to diagnosis and resources.

[1]  Marko Robnik-Sikonja,et al.  Theoretical and Empirical Analysis of ReliefF and RReliefF , 2003, Machine Learning.

[2]  B. Patterson,et al.  High-throughput cervical cancer screening using intracellular human papillomavirus E6 and E7 mRNA quantification by flow cytometry. , 2005, American journal of clinical pathology.

[3]  B. van Gemen,et al.  Application of the NASBA nucleic acid amplification method for the detection of human papillomavirus type 16 E6-E7 transcripts. , 1995, Journal of virological methods.

[4]  J. Val-Bernal,et al.  A type‐specific study of human papillomavirus prevalence in cervicovaginal samples in three different Spanish regions , 2009, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[5]  Chris H. Q. Ding,et al.  Minimum Redundancy Feature Selection from Microarray Gene Expression Data , 2005, J. Bioinform. Comput. Biol..

[6]  Joakim Dillner,et al.  Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. , 2008, Vaccine.

[7]  M. von Knebel Doeberitz,et al.  p16INK4a Immunohistochemistry Improves Interobserver Agreement in the Diagnosis of Cervical Intraepithelial Neoplasia , 2002, The American journal of surgical pathology.

[8]  Bernard Zenko,et al.  Evaluation Method for Feature Rankings and their Aggregations for Biomarker Discovery , 2009, MLSB.

[9]  A. Lie,et al.  Performance of Human Papillomavirus DNA and mRNA Testing Strategies for Women with and without Cervical Neoplasia , 2009, Journal of Clinical Microbiology.

[10]  A. Spathis,et al.  Clinical performance of human papillomavirus E6, E7 mRNA flow cytometric assay compared to human papillomavirus DNA typing. , 2011, Analytical and quantitative cytology and histology.

[11]  Jaideep Srivastava,et al.  Robust Feature Selection Technique Using Rank Aggregation , 2014, Appl. Artif. Intell..

[12]  E. Weiderpass,et al.  Triage of HR-HPV Positive Women with Minor Cytological Abnormalities: A Comparison of mRNA Testing, HPV DNA Testing, and Repeat Cytology Using a 4-Year Follow-Up of a Population-Based Study , 2014, PloS one.

[13]  M. Henry The Bethesda System 2001: an update of new terminology for gynecologic cytology. , 2003, Clinics in laboratory medicine.

[14]  J. Cuzick,et al.  Comparing the performance of six human papillomavirus tests in a screening population , 2013, British Journal of Cancer.

[15]  A. Thiébaut,et al.  Comparing human papillomavirus prevalences in women with normal cytology or invasive cervical cancer to rank genotypes according to their oncogenic potential: a meta-analysis of observational studies , 2013, BMC Infectious Diseases.

[16]  A. Bianco,et al.  Is HPV DNA testing specificity comparable to that of cytological testing in primary cervical cancer screening? Results of a meta‐analysis of randomized controlled trials , 2014, International journal of cancer.

[17]  Ronaldo C. Prati,et al.  Combining feature ranking algorithms through rank aggregation , 2012, The 2012 International Joint Conference on Neural Networks (IJCNN).