Use of the HPV MLPA assay in cervical cytology for the prediction of high grade lesions

Rogier J. N. T. M. Litjens, Wendy Theelen, Yvonne van de Pas, Jessica Ossel, Martin Reijans, Guus Simons, Ernst-Jan M. Speel, Brigitte F. M. Slangen, Frans C. S. Ramaekers, Roy F. P. M. Kruitwagen, Anton H. N. Hopman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Current screening methods for uterine cervical cancer such as Papanicolaou smears and/or high risk human Papillomavirus (HR-HPV) detection have a high negative predictive value but a low positive predictive value for the presence of high grade cervical lesions. Therefore, new parameters are needed to reduce the rate of unnecessary referrals for colposcopy. The predictive value of the HPV multiplex ligation-dependent probe amplification (MLPA) assay, which can assess simultaneously HPV16/18 viral load and viral integration, was evaluated. The assay was applied to 170 cervical cytological samples, and the results were correlated with the matching histological follow-up. The GP5+/6+ assay and qPCR were used as a control for HR-HPV typing. The MLPA assay classified a higher percentage of cases as high-risk (high-viral load and/or viral integration) with higher grades of dysplasia. There was a high correlation between the HPV MLPA assay and qPCR for viral load and HPV genotyping, and between the MLPA assay and the GP5+/6+ assay for HPV genotyping. The sensitivity and specificity of the HPV MLPA assay for the detection of high-grade lesions were 44% and 93%, respectively. This study demonstrates that the HPV MLPA assay can reliably detect HPV 16/18, viral load, and viral integration in cytological samples. Also, high-risk classification correlated well with the presence of high-grade dysplasia. However, for the implementation of the MLPA assay into clinical practice, additional HR-HPV types need to be included to increase the sensitivity of the assay, and thereby increase its negative predictive value.
Original languageEnglish
Pages (from-to)1386-1393
JournalJournal of Medical Virology
Volume85
Issue number8
DOIs
Publication statusPublished - Aug 2013

Keywords

  • cervical cancer
  • cytology
  • HPV
  • viral integration
  • PCR

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