Alterations in human papillomavirus-related biomarkers after treatment of cervical intraepithelial neoplasia

ObjectiveThis study aims to assess the alterations in various HPV-related biomarkers 6 months post-treatment and how these relate to various risk factors and individual characteristics; their role for the prediction of treatment failure was also evaluated.Material and methodsDesign: Prospective observational study.Population: Women planning to undergo treatment for cervical intraepithelial neoplasia.Intervention: A liquid-based cytology sample was taken pre-operatively. This was tested for HPV genotyping, Nucleic Acid Sequence Based Amplification, flow cytometric evaluation and p16 immunostaining. A repeat LBC sample was obtained 6 months post-treatment and was tested for the same biomarkers.Outcomes: The alterations of the biomarkers 6 months post-treatment were recorded. Their relation to individual characteristics and risk factors (age, smoking, sexual history, use of condom, CIN grade, excision margin status, crypt involvement) as well as their role for the prediction of residual/recurrent disease were assessed.Analysis: The accuracy parameters (sensitivity, specificity, positive and negative predictive value and the likelihood ratios) of each biomarker for the prediction of recurrent/residual CIN were calculated.ResultsA total of 190 women were recruited. All biomarkers had significantly higher negativity rates post-treatment compared to pre-treatment ones. Multivariate analysis demonstrated that consistent condom use post-treatment significantly reduces the high-risk HPV positivity rates in comparison to no use (OR = 0.18; 95% CI: 0.09-0.38). Sensitivity and specificity for all high risk HPV DNA testing were 0.5/0.62, respectively; the relevant values for only type 16 or 18 DNA typing were 0.5/0.92, for NASBA 0.5/0.94, for flow 0.5/0.85 and for p16 0.25/0.93.ConclusionCIN treatment reduces positivity for all HPV-related biomarkers. Consistent condom use significantly reduces high-risk HPV positivity rates. More cases of treatment failures are required in order to specify whether different combinations of HPV-related biomarkers could enhance the accuracy of follow up, possibly in the form of a Scoring System that could allow tailored post-treatment surveillance.

Research Highlights► There is a significant reduction in HPV related biomarkers' positivity rates after treatment for CIN. ► Apart from strict condom use no other factors were found to consistently affect biomarker (HPV DNA, mRNA, P16) status post-treatment. ► Assuming that negative biomarker status post-treatment is associated with lower recurrence rates, condom use after treatment should have a protective effect against recurrence. ► With the exception of HPV DNA testing, larger numbers of women are required to clarify the role of HPV related biomarkers in the follow up after treatment.