因此，在HPV感染的CIN患者中，早期检测HPV L1 蛋白的表达情况，有助于判断宫颈病变程度及其恶性进展趋势。CIN1和CIN2患者中L1（+）者早期治疗预后更好。

5．HPV L1衣壳蛋白检测的应用：CIN细胞逃脱机体细胞免疫系统的监视及清除功能，进而进展为癌[12]。因此，L1蛋白表达降低是显示HPV DNA被整合到宿主细胞的染色体上，来判断HPV感染是否能够引起良性或恶性病变的重要标志[13-14]。我们可以针对CIN患者进行检测并密切随访，有可能是一个潜在的预后判定的标志物[15]。

我们可以用免疫组化的方法检测宫颈细胞图片或组织切片。由于HPV L1衣壳蛋白为核蛋白，只有细胞核呈红色才是特异性阳性染色，一个红染的细胞核即可诊断为HPV L1阳性。我们联合应用宫颈细胞学、HPV-DNA、宫颈HPV L1蛋白检测及对患者分流。宫颈细胞学检测阴性的患者定期随访，阳性者检测HPV感染，有高危因素的人群则进一步检测HPV L1衣壳蛋白的表达。表达阳性者预后较好，建议行阴道镜检查，密切随访；表达阴性者则预后较差，建议立即行阴道镜活检密切随访，进行一步治疗。

6．L1蛋白的研究现状：由于HPV感染在宫颈癌病变患者中病因已经明确，为了有效的预防HPV感染与传播，研究人员开展了大量HPV疫苗的研究[16]。当前的疫苗主要以应用基因工程等技术开发多价VLPS或具有交叉保护活性的多个HPV型别的单组份疫苗。目的是在病毒感染前，阻止病毒侵入，疫苗产生中和抗体，直接对抗L1蛋白。研究中发现，疫苗对男性患者同样有预防的作用，接种疫苗的志愿者中，同性恋和异性恋的皮肤黏膜相关损害分别减少79%和92%以上[17]。

7．问题与展望：综上所述，随着宫颈组织损伤的逐渐加重，HPV L1的表达水平随之下降，发展至宫颈癌晚期几乎无病毒释放[18]。若中晚期宫颈癌局部病变控制良好，可以提高患者的生存率。但由于人群的遗传背景及生活环境的不同，肿瘤组织也存在高、低分化的差异，这可能影响L1的表达[19]。另外，HPV L1疫苗对于患者的接受能力及其临床应用价值需要进一步证实。我们认为：HPV L1疫苗不仅仅可以预防宫颈癌的发生，或许可以研究其分子靶向治疗，从而在临床工作中起到一定的治疗作用，有待于进一步的研究。HPV L1蛋白的检测，将有利于密切观察宫颈癌患者的发生发展过程，并提前预防和治疗病变，有望改善生活质量并延长生命。

参考文献

[1] Minosse C, Garbuglia AR, Lapa D, et al. Genetic variability in E6, E7 and L1 protein of HPV81 from HIV-1 positive women in Italy. New Microbiologica, 2010, 33(1):25-35.

[2] Chan PK, Liu SJ, Cheunq TH, et al. T-Cell Response to Human Papillomavirus Type 58 L1, E6, and E7 Peptides in Women with Cleared Infection, Cervical Intraepithelia Neoplasia, or Invasive Cancer. Clin and Vaccine immunol, 2010, 17(9):1315-1321.

[3] Lurchachaiwong W, Junyangdikul P, Payungporn S, et al. Relationship between Hybrid Capture II Ratios and DNA Amplification of E1, E6 and L1 Genes Used for the Detection of Human Papillomavirus in Samples with Different Cytological Findings. Asian Pac J Allergy Immunol, 2009, 27(4):217-224.

[4] Mahdavi A, Monk BJ. Vaccines against human papillomavirus and cervical cancer promises and challenges. Oncologist, 2005, 10(7):528-538.

[5] Hilfrich R, Hariri J. Prognostic relevance of human papillomavirus L1 capsid protein detection within mild and moderate dysplastic lesions of the cervix uteri in combination with p16 biomarker. Anal Quant Cytol Histol, 2008, 30(2):78-82.

[6] Michelli E, Téllez L, Mendoza JA, et al. Comparative analysis of three methods for HPV DNA detection in cervical samples. Invest Clin, 2011, 52(4):344-357.

[7] Gatta LB, Berenzi A, Balzarini P, et al. Diagnostic implications of L1, p16, and Ki-67 proteins and HPV DNA in low-grade cervical intraepithelial neoplasia. Int J Gynecol Pathol, 2011, 30(6):597-604.

[8] Stemberger-Papić S, Vrdoljak-Mozetic D, Ostojić DV, et al. Evaluation of the HPV L1 capsid protein in prognosis of mild and moderate dysplasia of the cervix uteri. Coll Antropol, 2010, 34(2):419-423.

[9] Arafa M, Boniver J, Delvenne P. Detection of HPV-induced cervical (pre) neoplastic lesions: a tissue micmarray (TMA) study. Appl Immunohistochem Mol Morphol, 2008, 16(5):422-432.

[10] 王伟，吴王飞，钱宁，等. HPV阳性宫颈细胞学标本及活检组织中L1蛋白表达及意义. 临床与实验病理学杂志, 2011, 27(9):985-987.

[11] Rauber D, Mehlhorn G, Fasching PA, et al. Prognostic significance of the detection of human papillomavirus L1 protein in smears of mild to moderate cervical intraepithelial lesions. Eur J Obstet Gynecol Reprod Biol, 2008, 140(2):258-262.

[12] Dijkstra MG, Heideman DA, van Kemenade FJ, et al. Brush-based self-sampling in combination with GP5+/6+-PCR-based hrHPV testing: High concordance with physician-taken cervical scrapes for HPV genotyping and detection of high-grade CIN . J Clin Virol, 2012, 54(2):147-151.

[13] Deschuyteneer M, Elouahabi A, Plainchamp D, et al. Molecular and structural characterization of the L1 virus-like particles that are used as vaccine antigens in Cervarix™, the AS04-adjuvanted HPV-16 and -18 cervical cancer vaccine. Hum Vaccin, 2010, 6(5):407-419.

[14] Kalantari M, Chase DM, Tewari KS, et al. Recombination of human papillomavirus-16 and host DNA in exfoliated cervical cells: a pilot study of L1 gene methylation and chromosomal integration as biomarkers of carcinogenic progression. J Med Virol, 2010, 82(2):311-320.

[15] Yu L, Wang L, Zhong J, et al. Diagnostic value of P16INK4A，Ki-67, and human papillomavirus L1 capsid protein immunochem- ical staining on cell blocks from residusk liquid based gynecologic cytology specimens. Cancer Cytopathol, 2010, 118(1):47 -55.

[16] Matić S, Masenga V, Poli A, et al. Comparative analysis of recombinant Human Papillomavirus 8 L1 production in plants by a variety of expression systems and purification methods. Plant Biotechnol J, 2012, 10(4):410-421.

[17] Giuliano AR, Palefsky JM, Goldstone S, et al. Efficacy of quadrivalent HPV vaccine against HPV infection and disease in males. N Engl J Med, 2011, 364(5):401-411.

[18] Sarmadi S, Izadi-mood N, Pourlashkari M, et al. HPV L1 capsid protein expression in squamous intraepithelial lesions of cervix uteri and its relevance to disease outcome. Arch Gynecol Obstet, 2012, 285(3):779-784.

[19] Tomesello ML, Losito S, Benincass G, et al. Human papillomavirus (HPV) genotypes and HPV16 variants and risk of adenocarcinoma and squamous cell carcinoma of the cervix. Gynecol Oncol, 2011, 121(1):32-34. 返回搜狐，查看更多