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Abstract：
We aimed to determine the frequency of human papillomavirus-independent (HPVI) cervical squamous cell carcinoma (SCC) and to describe clinicopathologic characteristics. Among 670 patients with surgically treated SCCs in an established multi-institutional cohort, 447 had available tissue. Tissue microarrays were constructed and studied by in situ hybridization (ISH) for high-risk and low-risk human papillomavirus (HPV) mRNA and immunohistochemistry for p16 and p53. Tumors were HPVI if negative by HPV ISH and they failed to show diffuse p16 positivity by immunohistochemistry, and human papillomavirus-associated (HPVA) if positive by HPV ISH. Ten HPVI SCCs and 435 HPVA SCCs were identified; 2 cases were equivocal and excluded from analysis. The overall rate of HPVI SCC was low (2%) but was higher among older patients (7% in patients above 60 y of age and 17% in patients above 70 y of age). Compared with HPVA, patients with HPVI SCC were significantly older (median age, 72 vs. 49, P <0.001) and diagnosed at a higher stage (40% vs. 18% with stage III/IV disease, P =0.055). p53 expression was varied; 2 cases (20%) had null expression and 8 (80%) had wild-type expression. HPVI SCCs were heterogenous, with keratinizing, nonkeratinizing, and warty morphologies observed. Several cases had a precursor lesion reminiscent of differentiated vulvar intraepithelial neoplasia, with prominent basal atypia and hypereosinophilia or a basaloid-like morphology. Two patients (20%) had distant recurrences within 12 months, and 3 (30%) died of disease during follow-up. HPVI SCCs are rare tumors that are more common among older patients with higher stage disease and have important clinical and histologic differences from HPVA SCCs.
摘要：
我们旨在确定人乳头瘤病毒非依赖性（HPVI）宫颈鳞状细胞癌（SCC）的发生频率并描述临床病理特征。在已建立的多机构队列中，670例经手术治疗的SCC患者中，447有可用的组织。构建了组织微阵列，并通过原位杂交（ISH）研究了高风险和低风险的人乳头瘤病毒（HPV）mRNA以及p16和p53的免疫组织化学。如果HPVISH阴性，则肿瘤为HPVI，并且通过免疫组织化学未能显示弥漫性p16阳性，和人乳头瘤病毒相关（HPVA），如果HPVISH阳性。确定了10例HPVISCC和435例HPVASCC；2例模棱两可，排除在分析之外。HPVISCC的总体发生率较低（2%），但在老年患者中更高（60岁以上患者为7%，70岁以上患者为17%）。与HPVA相比，HPVISCC患者明显年龄较大(中位年龄，72vs.49，P<0.001），并在较高的阶段诊断（40％vs.18％患有III/IV期疾病，P=0.055)。p53表达不同；2例（20％）表达无效，8例（80％）表达野生型。HPVISCC是异质的，角质化，非角质化,观察到疣状的形态。几例患者的前兆病变让人联想到分化型外阴上皮内瘤变，具有突出的基底异型性和嗜酸性粒细胞增多或基底细胞样形态。两名患者（20%）在12个月内出现远处复发，3（30％）在随访期间死于疾病。HPVISCC是罕见的肿瘤，在晚期疾病的老年患者中更为常见，并且与HPVASCC具有重要的临床和组织学差异。
