Circulating cell-free DNA (cfDNA) has attracted attention as a non-invasive biomarker for diagnosing and monitoring various cancers. Given that human papillomavirus (HPV) DNA integration and overexpression of E6/E7 oncogenes are pivotal events for carcinogenesis, we sought to determine if HPV E7 cfDNA could serve as a specific biomarker for cervical cancer detection. We applied droplet digital PCR (ddPCR) to quantify HPV16/18 E7 cfDNA from the serum of patients with cervical cancer, cervical intraepithelial neoplasia, and controls. HPV16/18 E7 cfDNA was highly specific for cervical cancer, displaying 30.77% sensitivity, 100% specificity, and an area under the curve of 0.65. Furthermore, we developed a sensitive isothermal detection of HPV16/18 E7 and the PIK3CA WT reference gene based on recombinase polymerase amplification combined with a lateral flow strip (RPA-LF). The assay took less than 30 min and the detection limit was 5–10 copies. RPA-LF exhibited 100% sensitivity and 88.24% specificity towards HPV16/18 E7 cfDNA in clinical samples. The agreement between RPA-LF and ddPCR was 83.33% ( κ = 0.67) for HPV16 E7 and 100% ( κ = 1.0) for HPV18 E7, indicating a good correlation between both tests. Therefore, we conclude that HPV E7 cfDNA represents a potential tumor marker with excellent specificity and moderate sensitivity for minimally invasive cervical cancer monitoring. Moreover, the RPA-LF assay provides an affordable, rapid, and ultrasensitive tool for detecting HPV cfDNA in resource-limited settings.

The aim of this study was to determine the prognostic impact of histological type among squamous cell carcinoma (SCC), adenocarcinoma (AC) and adenosquamous carcinoma (ASC) on the treatment outcome of early-stage cervical cancer patients after radical hysterectomy. The cohort comprised of 626 patients, diagnosed with stages IA2-IB1 cervical cancer between 1987 and 2013. Four hundred and one patients had SCC, 190 had AC and 35 had ASC. The 5-year disease-free survival (DFS) rates for AC, SCC and ASC were 89.3% (95%CI 83.2-93.2), 88.7% (95%CI 84.8-91.7) and 82.1% (95%CI 61.9-92.2), respectively (p = .594). In multivariate analyses, only older age and deep stromal invasion were statistically significantly associated with DFS, whereas histologic cell type was not (p = .524). Subgroup analysis showed that in the intermediate-high-risk groups, the SCC group had a significantly longer DFS, compared with the AC group or the ASC group (p = .001) while there was no DFS difference in the low-risk group. We believe that histologic cell type had no impact in low-risk early-stage cervical cancer patients. However, in the intermediate-high-risk groups, SCC is a more favourable factor for survival than AC/ASC.

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