Rosing Fabian, Plath Michaela, Proctor Tanja, Höfler Daniela, Alt Yvonne, Lucena-Porcel Carlota, Waterboer Tim, Hess Jochen, Plath Karim, Schroeder Lea
Division of Infections and Cancer Epidemiology, Immunology, Infection & Cancer Research Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Section Experimental and Translational Head and Neck Oncology, Department of Otolaryngology, Head and Neck Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Oral Oncol. 2025 Apr;163:107225. doi: 10.1016/j.oraloncology.2025.107225. Epub 2025 Mar 5.
The incidence rate of human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) is increasing. Despite good prognosis, recurrence can decrease health-related quality of life and increase mortality, so post-treatment monitoring is important for patient outcomes. One potential biomarker for post-treatment monitoring is HPV cell-free DNA (cfDNA) from blood plasma.
Plasma samples at start of treatment and during follow-up from 27 OPSCC patients were analyzed for cfDNA of six high-risk HPV types using a multiplex digital PCR assay. Presence of HPV cfDNA was compared to HPV tumor status determined by p16 immunohistochemistry, HPV DNA, HPV RNA and HPV16 E6 serology.
At start of treatment, sensitivity of HPV cfDNA detection in HPV-driven OPSCC cases was 89 % (17/19), while specificity was 100 % among 39 plasma samples from 8 HPV-negative OPSCC cases. A median of 4 follow-up plasma samples per patient over a mean time of 11 months were available. Positive and negative predictive values during follow-up were assessed on a per-test-basis. HPV cfDNA testing after completion of therapy had a positive predictive value of 100 % for HPV-OPSCC recurrence within one year, and a negative predictive value of 98 %. In cases of recurrent HPV-driven OPSCC, HPV cfDNA was detectable between 3 and 6.8 months before detection of recurrence by routine follow-up examination methods.
Post-treatment monitoring for early detection of recurrence could be aided by testing for HPV cfDNA in HPV-driven OPSCC patients.
人乳头瘤病毒（HPV）驱动的口咽鳞状细胞癌（OPSCC）发病率正在上升。尽管预后良好，但复发会降低与健康相关的生活质量并增加死亡率，因此治疗后监测对患者预后很重要。血浆中HPV游离DNA（cfDNA）是治疗后监测的一种潜在生物标志物。
使用多重数字PCR检测法对27例OPSCC患者治疗开始时及随访期间的血浆样本进行6种高危HPV类型的cfDNA分析。将HPV cfDNA的存在情况与通过p16免疫组织化学、HPV DNA、HPV RNA和HPV16 E6血清学确定的HPV肿瘤状态进行比较。
治疗开始时，HPV驱动的OPSCC病例中HPV cfDNA检测的敏感性为89%（17/19），而在8例HPV阴性OPSCC病例的39份血浆样本中特异性为100%。每位患者平均随访11个月，中位数为4份随访血浆样本。随访期间的阳性和阴性预测值按每次检测进行评估。治疗完成后HPV cfDNA检测对一年内HPV-OPSCC复发的阳性预测值为100%，阴性预测值为98%。在复发性HPV驱动的OPSCC病例中，在通过常规随访检查方法检测到复发前3至6.8个月可检测到HPV cfDNA。
对HPV驱动的OPSCC患者进行HPV cfDNA检测有助于治疗后监测以早期发现复发。
