Circulating tumor DNA (ctDNA) as a pan-cancer screening test: is it finally on the horizon?

The detection of cancer at an early stage while it is curable by surgical resection is widely believed to be one of the most effective strategies for reducing cancer mortality. Hence, the intense interests in the development of a simple pan-cancer screening test. Lack of sensitivity and specificity when combined with the low prevalence of most types of cancer types in the general population limit the use of most of the existing protein biomarkers for this purpose. Like proteins, tumor DNA also can be released into the circulation. Such circulating tumor DNA (ctDNA) can be differentiated from normal cell DNA by the presence of specific genetic alteration such as mutations, copy number changes, altered methylation patterns or being present in different sized fragments. Emerging results with test such as CancerSEEK or GRAIL suggest that the use of ctDNA can detect cancer with specificities >99%. Sensitivity however, is cancer type and stage-dependent, varying from approximately 40% in stage I disease to approximately 80% in stage III disease. It is important to stress however, that most of the studies published to date have used patients with an established diagnosis of cancer while the control population were healthy individuals. Although the emerging results are promising, evidence of clinical utility will require demonstration of reduced mortality following evaluation in a prospective randomized screening trial.

A Retrospective Cohort Study of Young Women Spontaneously Choosing to Be Vaccinated against HPV: Outcomes from Their First Cervical Cancer Screening Test

Background: Efficacy for cervical cancer prevention of opportunistic HPV vaccination in post-pubertal girls is lower than in 11-year-olds. Methods: Women born between 1986 and 1992 vaccinated at 15–25 years of age (at least one dose of 4-valent HPV vaccine) and screened at 24–27 years of age were included. Frequency of opportunistic vaccination, overall and by birth cohort, was calculated; screening outcomes were compared between vaccinated and unvaccinated women. Results: Overall, 4718 (4.9%) HPV-vaccinated, and 91,512 unvaccinated, women were studied. The frequency of vaccination increased by birth cohort, ranging between 1.8% and 9.8%; age at vaccination decreased progressively by birth cohort (p < 0.0001). Participation in screening was 60.8% among vaccinated, and 56.6% among unvaccinated, women (p < 0.0001). Detection rates (DR) for high-grade lesions were lower in vaccinated women (2.11‰ vs. 3.85‰ in unvaccinated, for CIN3+, p = 0.24; 0.0‰ vs. 0.22‰ for cancer). The DR of CIN3+ increased with age at vaccination, scoring respectively 0.0‰, 0.83‰, and 4.68‰ for women vaccinated when they were 15–16, 17–20, and 21–25 years old (p = 0.17). Conclusions: In comparison to unvaccinated women, higher compliance with cervical cancer screening invitation and lower CIN3+ DR among vaccinated women was observed. Age at vaccination was inversely correlated to vaccination efficacy.