Sensitive detection of human papillomavirus in cervical, head/neck, and schistosomiasis-associated bladder malignancies
Sensitive detection of human papillomavirus in cervical, head/neck, and schistosomiasis-associated bladder malignancies
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DOI：
10.1073/pnas.0406904102
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发表时间：
2005-05-24
影响因子：
11.1
通讯作者：
Kurnit, DM
中科院分区：
文献类型：
--
作者：
Yang, H;Yang, K;Kurnit, DM
我们检测了血吸虫病导致的宫颈癌、头颈癌或膀胱癌患者的血清和/或外周血成分 (PBF) 中是否存在人乳头瘤病毒 (HPV) DNA。使用质谱法与竞争性 PCR 相结合，通过“Mass-ARRAY”测定法在单个分子水平上检测到 HPV DNA。由此产生的灵敏度优于基于实时荧光 PCR 的检测，同时保持了特异性。我们的主要发现是：（i）几乎所有测试的宫颈癌和血吸虫病相关膀胱癌以及多种头/颈癌都与肿瘤中的 HPV DNA 相关。 (ii) 所有 27 例由血吸虫病引起的膀胱癌均与 HPV-16 DNA 的存在相关，该 DNA 可以在肿瘤和血清中检测到，但不能在 PBF 中检测到。相比之下，7 名血吸虫病相关膀胱癌患者在手术切除肿瘤后未检测到血清 HPV-16 DNA 信号。 (iii) 在我们研究的头颈癌中，前部肿瘤比后部肿瘤更常与肿瘤、血清和/或 PBF 中的 HPV DNA 相关。 (iv) 在宫颈癌中，所有肿瘤都含有 HPV DNA，通常可以在血清和/或 PBF 中检测到病毒 DNA。此外，在大多数未经治疗的高度宫颈不典型增生患者的血清和/或PBF中检测到HPV-16 DNA，但如果消除不典型增生，则HPV-16 DNA消失。灵敏、特异和定量的 Mass-ARRAY 技术应该能够监测癌症的发生、治疗以及与 HPV DNA 相关的恶性肿瘤和不典型增生的复发。
We assayed for the presence of human papilloma virus (HPV) DNA in serum and/or peripheral blood fraction (PBF) of individuals with cervical, head/neck, or bladder cancer due to schistosomiasis. Using mass spectroscopy coupled with competitive PCR, HPV DNA was detected at the individual molecule level by using "Mass-ARRAY" assays. The resultant sensitivity was superior to real-time fluorescent PCR-based assays, while specificity was maintained. Our principal findings were: (i) Virtually all tested cervical cancers and schistosomiasis-associated bladder cancers, and a plurality of head/neck cancers, are associated with HPV DNA in the tumor. (ii) All 27 bladder cancers due to schistosomiasis were associated with the presence of HPV-16 DNA, which can be detected in tumor and serum but not in PBF. In contrast, no serum HPV-16 DNA signal was detected in seven individuals with schistosomiasis-associated bladder cancers after surgical removal of the tumor. (iii) Among the head/neck cancers we studied, anterior tumors were more often associated with HPV DNA in tumor, serum, and/or PBF than posterior tumors. (iv) In cervical cancer, where all tumors contain HPV DNA, viral DNA could be detected often in serum and/or PBF. Further, HPV-16 DNA was detected in serum and/or PBF of most patients with untreated high-grade cervical dysplasia but disappeared if the dysplasia was eliminated. The sensitive, specific, and quantitative Mass-ARRAY technique should make it feasible to monitor cancer occurrence and treatment and recurrence of malignancies and dysplasias associated with HPV DNA.