Roden Richard B S, Monie Archana, Wu T-C
Departments of Pathology, The Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Curr Mol Med. 2007 Aug;7(5):490-503. doi: 10.2174/156652407781387127.
Human papillomavirus (HPV) is a causal agent for approximately 5.3% of cancers worldwide, including cervical cancer, and subsets of genital and head and neck cancer. Persistent HPV infection is a necessary, but not sufficient, cause of cervical cancer. Of the >100 HPV genotypes, only about a dozen, termed "high-risk", are associated with cancer. HPV-16 is present in approximately 50% of all cervical cancers and HPV-16, HPV-18, HPV-31 and HPV-45 together account for approximately 80%. Most high-risk HPV infections are subclinical, and are cleared by the host's immune system. The remainder produces low or high-grade squamous intraepithelial lesions (SILs), also called cervical intraepithelial neoplasia (CIN), which also may regress spontaneously. However persistent high grade SIL represents the precursor lesion of cervical cancer and carcinogenic progression is associated with integration of the viral DNA, loss of E2 and upregulation of viral oncogene expression, and chromosomal rearrangements like 3q gain. Cytologic screening of the cervix for SIL and intervention has reduced the incidence of cervical cancer in the US by an estimated 80% and HPV viral DNA and other molecular tests may improve screening further. The licensure of a preventive HPV vaccine ushers in a new era, but issues remain, including: protection restricted to a few oncogenic HPV types, access in low resource settings and impact on current cytologic screening protocols. Importantly, preventive HPV vaccination does not help with current HPV infection or disease. Here we examine the potential of second-generation preventive HPV vaccines and therapeutic HPV vaccination to address these outstanding issues.
人乳头瘤病毒（HPV）是全球约5.3%癌症的致病因素，包括宫颈癌以及部分生殖器癌和头颈癌。持续的HPV感染是宫颈癌的必要但非充分病因。在100多种HPV基因型中，只有大约12种被称为“高危型”，与癌症相关。约50%的宫颈癌中存在HPV-16，HPV-16、HPV-18、HPV-31和HPV-45共同约占80%。多数高危型HPV感染是亚临床的，可被宿主免疫系统清除。其余感染则会产生低级别或高级别鳞状上皮内病变（SIL），也称为宫颈上皮内瘤变（CIN），这些病变也可能自发消退。然而，持续的高级别SIL是宫颈癌的前驱病变，致癌进展与病毒DNA整合、E2缺失、病毒癌基因表达上调以及3q增益等染色体重排有关。针对SIL对宫颈进行细胞学筛查及干预已使美国宫颈癌发病率估计降低了80%，HPV病毒DNA及其他分子检测可能会进一步改善筛查效果。预防性HPV疫苗的获批开启了一个新时代，但问题依然存在，包括：保护范围仅限于少数致癌HPV类型、在资源匮乏地区的可及性以及对当前细胞学筛查方案的影响。重要的是，预防性HPV疫苗接种对当前HPV感染或疾病并无帮助。在此，我们探讨第二代预防性HPV疫苗和治疗性HPV疫苗解决这些突出问题的潜力。
