Advertisement

Prognostic Biomarker for Progression of Moderate Cervical Dysplasia

Advertisement

Key Points

  • The DNA methylation panel—the S5-classifier—was best able to identify which women with moderate dysplasia are actually at high risk of their disease going on to severe dysplasia.
  • When cytology, human papillomavirus (HPV) 16/18- and HPV16/31/33-genotyping, and S5 at baseline were compared to outcomes, S5 was the strongest biomarker associated with disease regression vs progression.
  • S5 alone or in combination with HPV genotyping showed increased sensitivity vs cytology when comparing regression vs persistence/progression.

In a study published by Louvanto et al in Clinical Infectious Diseases, researchers investigated the ability of a DNA methylation panel to determine between disease progression and regression among women of childbearing age with untreated cervical intraepithelial dysplasia.

In the majority of cases, moderate cervical dysplasia (also called cervical intraepithelial neoplasia 2, or CIN2) will resolve itself, but some women with the condition will go on to develop cervical cancer. Women with moderate dysplasia may face a choice between undergoing prompt treatment or short-term surveillance.

Women with moderate dysplasia may be advised to undergo surgery without delay, but this has a risk for the outcome of future pregnancies, including miscarriages and premature deliveries. Until now, there has been no test to show whether their cervical disease will progress.

Study Methods and Findings

The clinical study involved 149 women in Finland aged about 26 years old with identified CIN2. Researchers looked at different options for these young women and found that the DNA methylation panel—the S5 classifier—was best able to identify which women with moderate dysplasia are actually at high risk of their disease going on to severe dysplasia (or CIN3).

When cytology, human papillomavirus (HPV) 16/18- and HPV16/31/33-genotyping, and S5 at baseline were compared to outcomes, S5 was the strongest biomarker associated with disease regression vs progression. S5 alone or in combination with HPV genotyping showed increased sensitivity vs cytology when comparing regression vs persistence/progression. The highest area under the curve was 0.735 (95% confidence interval = 0.621–0.849) in the regression vs progression outcome with a combination of S5 and cytology—HPV genotyping did not provide additional prognostic information.

The researchers hope that this discovery will lead to a change in practice, with more active surveillance and fewer surgical interventions.

Senior study author Attila Lorincz, PhD, said in a press release, “It is scary for young women with a potentially serious dysplasia to be told that they may get cancer if they do not undergo surgery. Unfortunately, surgery can lead to a painful and distressing recovery period. In future pregnancies, there are substantially higher rates of miscarriage, infection, or premature delivery for mothers, as well as many risks for the fetus. Our study shows that most women with moderate dysplasia can be followed without treatment until their disease regresses. This gives the women a better chance for easy and safe pregnancies in the future.”

The DNA methylation test is currently under development, and more studies in different countries will need to take place as the test moves into routine use.

Disclosure: For full disclosures of the study authors, visit academic.oup.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


Advertisement

Advertisement



Advertisement