Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Vanderbilt University Hospital, Room 3020D 1121 Medical Center Drive, Nashville, TN, 37232-2561, USA.
Department of Otolaryngology - Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
Head Neck Pathol. 2021 Dec;15(4):1089-1098. doi: 10.1007/s12105-021-01318-4. Epub 2021 Apr 2.
Oropharyngeal squamous cell carcinoma (SCC) is increasing in incidence and, in Western countries, strongly associated with transcriptionally-active high-risk human papillomavirus (HPV). Within HPV-positive tumors, there is wide morphologic diversity with numerous histologic subtypes of SCC. There are also variable degrees of keratinization, anaplasia, stromal fibrosis, and maturing squamous differentiation. Unlike in the uterine cervix, where associations between HPV types and lineages/sublineages within types have been investigated with some clear correlations identified, little to no data exists for oropharyngeal SCC. In this study, for a large cohort of oropharyngeal SCC patients, we performed RTPCR for high-risk HPV. For the HPV positive patients, we sequenced the DNA of the entire HPV16 genome and determined lineages and sublineages, correlating HPV status, genotype, and HPV16 lineages/sublineages with SCC subtype and various histologic features. Of the 259 patients, 224 (86.5%) were high-risk HPV positive, of which 210/224 (93.8%) were HPV type 16 and 6/224 (2.7%) HPV type 33. Of the four HPV16 lineages, A was the most frequent (192/214 or 89.8%) and of the HPV16 A sublineages, A1 was the most frequent (112/210 or 53.3%). Patients with HPV negative tumors were more often keratinizing vs other types (23/35 or 65.7%) and thus more likely to have more maturing squamous differentiation and stromal desmoplasia. There was no significant correlation between HPV type (16 versus other), between HPV16 lineage (A versus others), or HPV16 A sublineages (A1 or A2 versus others) and morphologic type of SCC nor the various morphologic features of anaplasia/multinucleation, degree of keratinization, nor amount of stromal desmoplasia. In summary, in our cohort, there was no correlation between the type of HPV, the HPV 16 lineage or sublineage, and any of the histologic features or morphologic SCC subtypes.
口咽鳞状细胞癌（SCC）的发病率正在上升，在西方国家，它与转录活跃的高危型人乳头瘤病毒（HPV）密切相关。在 HPV 阳性肿瘤中，存在着广泛的形态多样性，有许多 SCC 的组织学亚型。也存在着不同程度的角化、异形性、间质纤维化和成熟的鳞状分化。与子宫颈不同，在那里已经对 HPV 类型与类型内的谱系/亚谱系之间的关联进行了一些明确的相关性研究，但对于口咽 SCC 几乎没有数据。在这项研究中，我们对一大群口咽 SCC 患者进行了 RT-PCR 检测高危型 HPV。对于 HPV 阳性患者，我们对整个 HPV16 基因组进行了 DNA 测序，并确定了谱系和亚谱系，将 HPV 状态、基因型和 HPV16 谱系/亚谱系与 SCC 亚型和各种组织学特征相关联。在 259 名患者中，224 名（86.5%）为高危型 HPV 阳性，其中 210 名（93.8%）为 HPV 16 型，6 名（2.7%）为 HPV 33 型。在四个 HPV16 谱系中，A 型最为常见（192/214 或 89.8%），在 HPV16 A 亚谱系中，A1 型最为常见（112/210 或 53.3%）。HPV 阴性肿瘤患者的角化程度比其他类型更常见（23/35 或 65.7%），因此更有可能具有更成熟的鳞状分化和间质纤维变性。HPV 类型（16 型与其他类型）、HPV16 谱系（A 型与其他谱系）或 HPV16 A 亚谱系（A1 或 A2 与其他亚谱系）与 SCC 的形态类型之间，以及异形性/多核化、角化程度或间质纤维变性的各种形态特征之间均无显著相关性。总之，在我们的队列中，HPV 类型、HPV16 谱系或亚谱系与任何组织学特征或形态 SCC 亚型之间均无相关性。
