Institute Clinic of Gynecology, Obstetrics, and Neonatology, Hospital Clínic - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Department of Pathology, Hospital Clínic, University of Barcelona, Barcelona, Spain.
Mod Pathol. 2020 Jan;33(1):128-137. doi: 10.1038/s41379-019-0360-3. Epub 2019 Sep 6.
Human papillomaviruses (HPVs) are the causative agents of carcinoma of the uterine cervix. A number of HPV genotypes have been associated with cervical cancer and almost all tumors associated with HPV show strong p16 expression. However, there is little information on the possible impact of the HPV genotype and p16 immunostaining on the clinicopathological features or their prognostic value in cervical carcinoma. We evaluated a series of 194 patients with HPV-positive cervical cancers treated at our institution, focusing on the clinicopathological features and the relationship of the HPV genotypes and p16 immunostaining with the prognosis. A single HPV type was identified in 149 (77%) tumors, multiple HPV infection was detected in 30 cases (15%), and undetermined HPV type/s were identified in 15 (8%) carcinomas. HPV 16 and/or 18 were detected in 156 (80%) tumors. p16 was positive in 186 (96%) carcinomas, but eight tumors (4%) were negative for p16 (seven squamous cell carcinomas, one adenocarcinoma); 5/8 caused by HPV 16 and/or 18. Patients with HPV 16 and/or 18 were younger (49 ± 15 vs. 57 ± 17 years, p < 0.01) and more frequently had nonsquamous tumors than patients with other HPV types (24% [37/156] vs. 0% [0/38]; p = 0.01). Neither the HPV type nor multiple infection showed any prognostic impact. Patients with p16-negative tumors showed a significantly worse overall survival than women with p16-positive carcinomas (45 vs. 156 months, p = 0.03), although no significant differences in disease-free survival were observed. In the multivariate analysis, negative p16 immunostaining was associated with a worse overall survival together with advanced FIGO stage and lymph node metastases. In conclusion, the HPV genotype has limited clinical utility and does not seem to have prognostic value in cervical cancer. In contrast, a negative p16 result in patients with HPV-positive tumors is a prognostic marker associated with a poor overall survival.
人乳头瘤病毒（HPV）是宫颈癌的致病因子。许多 HPV 基因型与宫颈癌有关，几乎所有与 HPV 相关的肿瘤都显示出强烈的 p16 表达。然而，关于 HPV 基因型和 p16 免疫组化对宫颈癌临床病理特征的可能影响及其预后价值的信息很少。我们评估了在我们机构治疗的 194 例 HPV 阳性宫颈癌患者，重点关注临床病理特征以及 HPV 基因型和 p16 免疫组化与预后的关系。在 149 例（77%）肿瘤中确定了单一 HPV 类型，在 30 例（15%）中检测到多种 HPV 感染，在 15 例（8%）中确定了未确定的 HPV 类型/种。在 156 例（80%）肿瘤中检测到 HPV 16 和/或 18。186 例（96%）宫颈癌中 p16 阳性，但有 8 例（4%）p16 阴性（7 例鳞状细胞癌，1 例腺癌）；其中 5 例由 HPV 16 和/或 18 引起。HPV 16 和/或 18 患者比其他 HPV 类型患者年轻（49±15 岁 vs. 57±17 岁，p<0.01），更常发生非鳞状肿瘤（24%[37/156] vs. 0%[0/38]；p=0.01）。HPV 类型或多重感染均无预后影响。p16 阴性肿瘤患者的总生存明显差于 p16 阳性宫颈癌患者（45 个月 vs. 156 个月，p=0.03），但无疾病进展生存差异。在多变量分析中，p16 免疫组化阴性与 FIGO 分期较晚和淋巴结转移一起与总生存不良相关。总之，HPV 基因型在宫颈癌中的临床应用价值有限，似乎没有预后价值。相比之下，HPV 阳性肿瘤患者的 p16 阴性结果是与总生存不良相关的预后标志物。
