Posted on January 04, 2019
Women undergoing routine cervical cancer screening who test positive for human papillomavirus (HPV) infection or related cytologic (Pap) abnormalities, after a history of negative cotests, have very low risk of developing precancer or cancer from that new abnormality, according to researchers at the National Cancer Institute, Albert Einstein College of Medicine, and Kaiser Permanente Northern California. This study, published December 21, 2018, in the Journal of the National Cancer Institute, considers, for the first time, the impact of multiple negative cotests on the risk of precancer following a newly positive screen, and the results show a strong and progressive decrease in risk of all positive findings when they are preceded by negative cotests.
The impact of prior negative screening was seen for all subsequent abnormal results, even high-grade abnormalities. For example, the authors noted that women who screened newly positive for HPV and presented with positive, low-risk abnormalities (low-grade squamous intraepithelial lesions or atypical squamous cells of undetermined significance) had sufficiently low risk of developing precancer or cancer to consider a future recommendation of surveillance, rather than colposcopy (more intense visual inspection under magnification, with biopsy of visually suspicious lesions).
The findings confirm and reflect the natural history of HPV and cervical carcinogenesis. New infections with HPV, the virus that causes cervical cancer, are typically benign. The body manages the infection without acquiring cell changes that may go on to become cancerous. When infections persist over more than 1-2 years, the risk that they will result in precancer increases. The seriousness of a positive HPV-test, therefore, depends on whether it indicates a new infection or the persistence of a pre-existing one, and furthermore, determines a subsequent course of action. Screening guidelines prescribe clinical management based on the most recent test result and do not account for screening history, which often leads to over management of otherwise benign HPV infections.
The investigators conducted this study to assess the risk of cervical cancer or precancer associated with a positive HPV or abnormal cytology test after a screening history of consecutive negative co-tests. The study utilized data from Kaiser Permanente Northern California which included HPV screenings every 3 years, follow up, and treatment of over a million women over the age of 30 between 2003 and 2015.
Future research is needed to validate these findings in diverse populations. Additionally, since this study focused only on completely negative screening histories, future studies can address questions of complex screening histories.
Castle PE et al. "Role of Screening History in Clinical Meaning and Optimal Management of Positive Cervical Screening Results." JNCI. December 21, 2018. DOI: 10.1093/jnci/djy192. [Epub ahead of print]