Retrospective analysis of negative cytology results correlated with a positive high-risk in the human papillomavirus result and subsequent results of patients over a period of three years.

This research paper evaluates the efficacy of co-testing in precluding cervical cancer, with a particular focus on distinguishable outcomes of the human papillomavirus (HPV) vs. cytology tests. A retrospective review of 5948 patients, who tested positive for high-risk HPV but showed negative cytologic findings, revealed that 15.006% tested positive in subsequent screenings. A comparative analysis of various commercial HPV tests highlighted the precision of mRNA-based HPV testing by Aptima (Hologic) in reducing the likelihood of false-negative cytology. The paper challenges the conviction that a negative cytology alone suffices advocating for a condensed testing interval in instances of positive HPV outcomes, thereby facilitating earlier intervention and optimal preventive care. These findings unveil an exigency for reconsidering preventive strategies based on test outcomes.

Towards early detection of cervical cancer: Fractal dimension of AFM images of human cervical epithelial cells at different stages of progression to cancer.

We used AFM HarmoniX modality to analyse the surface of individual human cervical epithelial cells at three stages of progression to cancer, normal, immortal (pre-malignant) and carcinoma cells. Primary cells from 6 normal strains, 6 cancer, and 6 immortalized lines (derived by plasmid DNA-HPV-16 transfection of cells from 6 healthy individuals) were tested. This cell model allowed for good control of the cell phenotype down to the single cell level, which is impractical to attain in clinical screening tests (ex-vivo). AFM maps of physical (nonspecific) adhesion are collected on fixed dried cells. We show that a surface parameter called fractal dimension can be used to segregate normal from both immortal pre-malignant and malignant cells with sensitivity and specificity of more than 99%. The reported method of analysis can be directly applied to cells collected in liquid cytology screening tests and identified as abnormal with regular optical methods to increase sensitivity. FROM THE CLINICAL EDITOR: Despite cervical smear screening, sometimes it is very difficult to differentiate cancers cells from pre-malignant cells. By using AFM to analyze the surface properties of human cervical epithelial cells, the authors were able to accurately identify normal from abnormal cells. This method could augment existing protocols to increase diagnostic accuracy.

Ultrabright fluorescent mesoporous silica nanoparticles for prescreening of cervical cancer.

We report on the first functional use of recently introduced ultrabright fluorescent mesoporous silica nanoparticles, which are functionalized with folic acid, to distinguish cancerous and precancerous cervical epithelial cells from normal cells. The high brightness of the particles is advantageous for fast and reliable identification of both precancerous and cancerous cells. Normal and cancer cells were isolated from three healthy women and three cancer patients. Three precancerous cell lines were derived by immortalization of primary cultures of normal cells with human papillomavirus type-16 (HPV-16) DNA. We observed substantially different particle internalization by normal and cancerous/precancerous cells after a short incubation time of 15 minutes. Compared to HPV-DNA and cell pathology tests, which are currently used for prescreening of cervical cancer, we demonstrated that the specificity of our method was similar (94-95%), whereas its sensitivity was significantly better (95-97%) than the sensitivity of those currently used tests (30-80%). FROM THE CLINICAL EDITOR: This team of investigators reports on the development of a new screening test for cervical cancer using ultrabright fluorescent mesoporous silica nanoparticles functionalized with folic acid, enabling significantly better sensitivity (95-97% vs. 30-80%) and maintained specificity (94-95%) compared with current clinical tests. This test should find a way to clinical use in the near future.