Unit of Cancer Epidemiology, Belgian Cancer Centre, Sciensano, Juliette Wytsmanstraat 14, 1050, Brussels, Belgium.
AMBIOR, Laboratory for Cell Biology & Histology, University of Antwerp, Antwerp, Belgium.
BMC Infect Dis. 2022 Aug 6;22(1):676. doi: 10.1186/s12879-022-07654-2.
The incidence of high-risk human papillomavirus (hrHPV)-driven head and neck squamous cell carcinoma, in particular oropharyngeal cancers (OPC), is increasing in high-resource countries. Patients with HPV-induced cancer respond better to treatment and consequently have lower case-fatality rates than patients with HPV-unrelated OPC. These considerations highlight the importance of reliable and accurate markers to diagnose truly HPV-induced OPC.
The accuracy of three possible test strategies, i.e. (a) hrHPV DNA PCR (DNA), (b) p16 immunohistochemistry (IHC) (p16), and (c) the combination of both tests (considering joint DNA and p16 positivity as positivity criterion), was analysed in tissue samples from 99 Belgian OPC patients enrolled in the HPV-AHEAD study. Presence of HPV E6*I mRNA (mRNA) was considered as the reference, indicating HPV etiology.
Ninety-nine OPC patients were included, for which the positivity rates were 36.4%, 34.0% and 28.9% for DNA, p16 and mRNA, respectively. Ninety-five OPC patients had valid test results for all three tests (DNA, p16 and mRNA). Using mRNA status as the reference, DNA testing showed 100% (28/28) sensitivity, and 92.5% (62/67) specificity for the detection of HPV-driven cancer. p16 was 96.4% (27/28) sensitive and equally specific (92.5%; 62/67). The sensitivity and specificity of combined p16 + DNA testing was 96.4% (27/28) and 97.0% (65/67), respectively. In this series, p16 alone and combined p16 + DNA missed 1 in 28 HPV driven cancers, but p16 alone misclassified 5 in 67 non-HPV driven as positive, whereas combined testing would misclassify only 2 in 67.
Single hrHPV DNA PCR and p16 IHC are highly sensitive but less specific than using combined testing to diagnose HPV-driven OPC patients. Disease prognostication can be encouraged based on this combined test result.
高危型人乳头瘤病毒（hrHPV）驱动的头颈部鳞状细胞癌，特别是口咽癌（OPC），在高资源国家的发病率正在上升。HPV 相关癌症患者对治疗的反应更好，因此病死率低于 HPV 无关的 OPC 患者。这些考虑因素强调了可靠和准确的标志物的重要性，以诊断真正的 HPV 诱导的 OPC。
在比利时 HPV-AHEAD 研究中纳入的 99 例 OPC 患者的组织样本中，分析了三种可能的检测策略的准确性，即（a）hrHPV DNA PCR（DNA），（b）p16 免疫组化（IHC）（p16），以及（c）联合两种检测方法（将联合 DNA 和 p16 阳性作为阳性标准）。存在 HPV E6*I mRNA（mRNA）被认为是 HPV 病因的标志物。
99 例 OPC 患者纳入研究，其 DNA、p16 和 mRNA 的阳性率分别为 36.4%、34.0%和 28.9%。95 例 OPC 患者的三种检测方法（DNA、p16 和 mRNA）均有有效结果。使用 mRNA 状态作为参考，DNA 检测对 HPV 驱动的癌症的检测灵敏度为 100%（28/28），特异性为 92.5%（62/67）。p16 的灵敏度为 96.4%（27/28），特异性相同（92.5%；62/67）。联合 p16+DNA 检测的灵敏度和特异性分别为 96.4%（27/28）和 97.0%（65/67）。在本系列中，p16 单独和联合 p16+DNA 漏诊了 28 例 HPV 驱动癌症中的 1 例，但 p16 单独将 67 例非 HPV 驱动癌症中的 5 例误诊为阳性，而联合检测只会将 67 例中的 2 例误诊。
单一的 hrHPV DNA PCR 和 p16 IHC 具有较高的灵敏度，但特异性低于联合检测，用于诊断 HPV 驱动的 OPC 患者。可以根据这种联合检测结果来鼓励疾病预后。
