Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
Department of Otolaryngology - Head & Neck surgery, Aarhus University Hospital, Aarhus, Denmark.
Acta Oncol. 2023 Nov;62(11):1384-1388. doi: 10.1080/0284186X.2023.2266127. Epub 2023 Nov 7.
The prognosis after primary (chemo-)radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) is affected by Human Papillomavirus (HPV) status, with a better prognosis in HPV-positive OPSCC. HPV-status is routinely assessed by p16 immunohistochemistry (IHC), but additional HPV DNA testing is debated. Also, there are numerous HPV genotypes, which prognostic role may need clarification. The purpose of this study was: (1) to test a custom-made targeted HPV next generation sequencing (NGS) panel in OPSCC, (2) to determine correlation with p16 IHC, and (3) to assess the impact of HPV DNA testing on outcome in the prospectively randomized clinical trial DAHANCA 19.
We included 271 patients with OPSCC treated with primary (chemo-)radiotherapy in the DAHANCA 19 trial. Of these, 199 (73%) were p16-positive. HPV-status was determined by targeted HPV next generation sequencing (NGS), using a custom-made HPV genotyping panel.
HPV was detected in 194 tumor samples. p16 IHC and NGS HPV status were concordant in 265 (98%) of 271 patients, whereas we did not detect HPV DNA in 5 p16-positive tumors. HPV16 accounted for 169 of 194 HPV-positive cases (87%). HPV genotypes 18, 31, 33, 35, and 59 were also detected.Loco-regional failure and overall survival were similar whether patients were separated by p16 IHC, or HPV DNA status ( < 0.0001 for all) and did not depend on HPV genotype ( = 0.9 and = 0.7).
In the present study, HPV DNA testing or typing in a Danish OPSCC cohort did not add additional information to p16 IHC, the most widely used and accepted prognostic indicator.
原发（放）化疗后口咽鳞状细胞癌（OPSCC）的预后受人类乳头瘤病毒（HPV）状态的影响，HPV 阳性 OPSCC 的预后较好。HPV 状态通常通过 p16 免疫组化（IHC）评估，但 HPV DNA 检测存在争议。此外，HPV 有多种基因型，其预后作用尚需阐明。本研究的目的是：（1）检测 OPSCC 中定制的靶向 HPV 下一代测序（NGS）面板，（2）确定与 p16 IHC 的相关性，（3）评估 HPV DNA 检测对前瞻性随机临床试验 DAHANCA 19 中结果的影响。
我们纳入了 DAHANCA 19 试验中 271 例接受原发（放）化疗的 OPSCC 患者。其中，199 例（73%）为 p16 阳性。通过使用定制的 HPV 基因分型面板的靶向 HPV NGS 来确定 HPV 状态。
在 271 例患者中的 194 例肿瘤样本中检测到 HPV。271 例患者中有 265 例（98%）的 p16 IHC 和 NGS HPV 状态一致，而在 5 例 p16 阳性肿瘤中未检测到 HPV DNA。194 例 HPV 阳性病例中有 169 例（87%）为 HPV16 型。还检测到 HPV 基因型 18、31、33、35 和 59。局部区域失败和总生存率无论通过 p16 IHC 还是 HPV DNA 状态（所有情况均 < 0.0001）进行分组均相似，且不依赖于 HPV 基因型（ = 0.9 和 = 0.7）。
在本研究中，在丹麦 OPSCC 队列中进行 HPV DNA 检测或分型并未为 p16 IHC（最广泛使用和接受的预后指标）提供额外信息。
