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复发性呼吸道乳头状瘤病中人类乳头瘤病毒、病毒载量及增殖率对α干扰素治疗的反应

Human papillomavirus, viral load and proliferation rate in recurrent respiratory papillomatosis in response to alpha interferon treatment.

作者信息

Szeps Michael, Dahlgren Liselotte, Aaltonen Leena-Maija, Öhd John, Kanter-Lewenshon Lena, Dahlstrand Hanna, Munck-Wikland Eva, Grandér Dan, Dalianis Tina

机构信息

Department of Oncology-Pathology, CancerCenterKarolinska, R8 : 01, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden.

Department of Oto-Rhino-Laryngology, Helsinki University Hospital, Helsinki, Finland.

出版信息

J Gen Virol. 2005 Jun;86(Pt 6):1695-1702. doi: 10.1099/vir.0.80849-0.

Abstract

The aim of this study was to identify recurrent respiratory papillomatosis patients who may benefit from interferon (IFN)-alpha treatment and to determine the means of IFN-alpha action. The presence of human papillomavirus (HPV) and viral load and proliferation rate in pre-, ongoing and post-treatment respiratory papillomatosis biopsies were examined retrospectively in 25 patients, 18 of whom were IFN-alpha treated and seven of whom were IFN-alpha non-treated. Using PCR, HPV was found to be present in 20/25 respiratory papillomatosis patients and HPV type was determined for 18/25 patients (12 HPV6 and six HPV11). Eighteen of the patients were treated with IFN-alpha, 14 of whom were HPV positive (eight HPV6, five HPV11 and one undefined HPV). Response to IFN-alpha therapy was observed in 12 patients (7/8 HPV6, 3/5 HPV11, 1/1 undefined HPV and 1/4 HPV negative), while six patients (1/8 HPV6, 2/5 HPV11 and 3/4 HPV negative) did not respond to therapy. Viral load, determined by quantitative real-time PCR (between 0.03 and 533 HPV copies per cell), and proliferation rate, determined as the percentage of Ki-67-positive cells (between 8 and 54 %), were similar in IFN-alpha-treated and non-treated patients and were generally unaffected by IFN-alpha treatment. In summary, most (12/18) IFN-alpha-treated patients responded to therapy. Moreover, there was a tendency for patients with HPV6-positive (7/8) respiratory papillomatosis to respond more frequently to IFN-alpha therapy than patients with HPV11 (3/5) or HPV-negative (1/4) respiratory papillomatosis. Finally, the presence of HPV and viral load and proliferation in respiratory papillomatosis biopsies was similar in patients treated or not with IFN-alpha and were in general unaffected by IFN-alpha treatment.

摘要

本研究的目的是识别可能从α干扰素(IFN)治疗中获益的复发性呼吸道乳头状瘤病患者,并确定α干扰素的作用方式。对25例复发性呼吸道乳头状瘤病患者治疗前、治疗期间和治疗后的活检组织进行回顾性检查,检测人乳头瘤病毒(HPV)的存在情况、病毒载量和增殖率,其中18例接受α干扰素治疗,7例未接受α干扰素治疗。通过聚合酶链反应(PCR)发现,25例复发性呼吸道乳头状瘤病患者中有20例存在HPV,25例患者中有18例确定了HPV类型(12例为HPV6,6例为HPV11)。18例患者接受了α干扰素治疗,其中14例HPV呈阳性(8例HPV6,5例HPV11,1例未明确的HPV)。12例患者(7/8 HPV6、3/5 HPV11、1/1未明确的HPV和1/4 HPV阴性)对α干扰素治疗有反应,而6例患者(1/8 HPV6、2/5 HPV11和3/4 HPV阴性)对治疗无反应。通过定量实时PCR测定的病毒载量(每细胞0.03至533个HPV拷贝)和以Ki-67阳性细胞百分比确定的增殖率(8%至54%)在接受α干扰素治疗和未接受治疗的患者中相似,且一般不受α干扰素治疗的影响。总之,大多数(12/18)接受α干扰素治疗的患者对治疗有反应。此外,HPV6阳性(7/8)的复发性呼吸道乳头状瘤病患者比HPV11(3/5)或HPV阴性(1/4)的复发性呼吸道乳头状瘤病患者更倾向于对α干扰素治疗有更频繁的反应。最后,接受或未接受α干扰素治疗的复发性呼吸道乳头状瘤病患者活检组织中HPV的存在情况、病毒载量和增殖情况相似,且一般不受α干扰素治疗的影响。

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