Center for Translational Research in Oncology, Instituto do Cancer do Estado de Sao Paulo ICESP, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo FMUSP HC, Sao Paulo, Brazil; Comprehensive Center for Precision Oncology, Universidade de Sao Paulo, São Paulo, Brazil.
Molecular Oncology Center, Hospital Sírio-Libanês, São Paulo, SP, Brazil.
Oral Oncol. 2024 Feb;149:106676. doi: 10.1016/j.oraloncology.2023.106676. Epub 2023 Dec 26.
HPV-16 driven oropharynx/oral cavity squamous cell carcinomas prevalence varies globally. We evaluated the presence of HPV-16 ctDNA and HPV-16 E6 antibodies in samples obtained from participants treated at the Instituto do Cancer do Estado de Sao Paulo, ICESP, and from whom tumoral HPV DNA, HPV-16 E6*I mRNA, and p16 status was also accessed.
HPV was genotyped by PCR-hybridization. All HPV DNA positive and ∼10 % HPV DNA negative cases underwent p16 immunohistochemistry and E6*I RNA testing using a multiplex bead based protocol. HPV-16 ctDNA and anti-E6 antibodies were assessed by ddPCR (digital droplet PCR) and multiplex serology, respectively.
The prevalence of HPV-16 in oropharynx carcinoma (OPC) cases was low (8.7 %) when considering solely HPV-16 DNA detection, and even lower (5.2 %) when taken into consideration the concomitant detection of HPV-16 E6*I RNA and/or p16 (HPV-16 attributable fraction - AF). None of the oral cavity cancer (OCC) cases were detected with HPV-16 DNA. HPV-16 ctDNA was more commonly detected than HPV-16 E6 antibodies (29.8 % versus 10.6 %). Both serum biomarkers attained 100 % sensitivity of detecting HPV-16 AF OPC, however the specificity of the HPV-16 anti-E6 biomarker was higher compared to ctDNA (93.2 % versus 75.0 %). Finally, when both HPV-16 ctDNA and anti-E6 biomarkers were considered together, the sensitivity and specificity for HPV-16 OPC detection was 100 % and about 70 %, respectively, independently of analyzing HPV-16 DNA positive or HPV-16 AF tumors.
Our findings corroborate that serum biomarkers are highly sensitive and specific biomarkers for detection of HPV-associated OPC.
HPV-16 驱动的口咽/口腔鳞状细胞癌的患病率在全球范围内存在差异。我们评估了在圣保罗州癌症研究所（ICESP）接受治疗的参与者的样本中 HPV-16 ctDNA 和 HPV-16 E6 抗体的存在情况，这些参与者的肿瘤 HPV DNA、HPV-16 E6*I mRNA 和 p16 状态也进行了评估。
通过 PCR-杂交对 HPV 进行基因分型。所有 HPV DNA 阳性和大约 10%的 HPV DNA 阴性病例进行了 p16 免疫组化和 E6*I RNA 测试，使用基于多重珠的方案。通过 ddPCR（数字 droplet PCR）和多重血清学分别评估 HPV-16 ctDNA 和抗 E6 抗体。
仅考虑 HPV-16 DNA 检测时，口咽癌（OPC）病例中 HPV-16 的患病率较低（8.7%），而考虑到 HPV-16 E6*I RNA 和/或 p16 的同时检测时（HPV-16 归因分数 - AF）则更低（5.2%）。没有口腔癌（OCC）病例被检测到 HPV-16 DNA。HPV-16 ctDNA 的检出率高于 HPV-16 E6 抗体（29.8%比 10.6%）。两种血清生物标志物对 HPV-16 AF OPC 的检测均具有 100%的敏感性，然而 HPV-16 抗 E6 生物标志物的特异性高于 ctDNA（93.2%比 75.0%）。最后，当同时考虑 HPV-16 ctDNA 和抗 E6 生物标志物时，HPV-16 OPC 检测的敏感性和特异性分别为 100%和约 70%，而与分析 HPV-16 DNA 阳性或 HPV-16 AF 肿瘤无关。
我们的发现证实了血清生物标志物是检测 HPV 相关 OPC 的高度敏感和特异的生物标志物。
