Brinkman J A, Caffrey A S, Muderspach L I, Roman L D, Kast W M
Norris Comprehensive Cancer Center, Keck/University of Southern California School of Medicine, Los Angeles, CA, USA.
Eur J Gynaecol Oncol. 2005;26(2):129-42.
Cervical cancer is the second most common cause of cancer-related deaths in women worldwide. Screening for cervical cancer is accomplished utilizing a Pap smear and pelvic exam. While this technology is widely available and has reduced cervical cancer incidence in industrialized nations, it is not readily available in third world countries in which cervical cancer incidence and mortality is high. Development of cervical cancer is associated with infection with high risk types of human papillomavirus (HPV) creating a unique opportunity to prevent or treat cervical cancer through anti-viral vaccination strategies. Several strategies have been examined in clinical trials for both the prevention of HPV infection and the treatment of pre-existing HPV-related disease. Clinical trials utilizing prophylactic vaccines containing virus-like particles (VLPs) indicate good vaccine efficacy and it is predicted that a prophylactic vaccine may be available within the next five years. But, preclinical research in this area continues in order to deal with issues such as cost of vaccination in underserved third world populations. A majority of clinical trials using therapeutic agents which aim to prevent the progression of pre-existing HPV associated lesions or cancers have shown limited efficacy in eradicating established tumors in humans possibly due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Future trends in clinical trials with therapeutic agents will examine patients with early stage cancers or pre-invasive lesions in order to prevent invasive cervical cancer. Meanwhile, preclinical studies in this field continue and include the further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. Given that cervical cancers are caused by the human papillomavirus, the prospect of therapeutic vaccination to treat existing lesions and prophylactic vaccination to prevent persistent infection with the virus are high and may be implemented in the near future. The consequences for clinical management may include a significant reduction in the frequency of Pap smear screening in the case of prophylactic vaccines, and the availability of less invasive and disfiguring treatment options for women with pre-existing HPV associated lesions in the case of therapeutic vaccines. Implementation of both prophylactic and therapeutic vaccine regimens could result in a significant reduction of health care costs and reduction of worldwide cervical cancer incidence.
宫颈癌是全球女性癌症相关死亡的第二大常见原因。宫颈癌筛查通过巴氏涂片检查和盆腔检查来完成。虽然这项技术在工业化国家广泛可用且降低了宫颈癌发病率，但在宫颈癌发病率和死亡率较高的第三世界国家却难以普及。宫颈癌的发生与高危型人乳头瘤病毒（HPV）感染有关，这为通过抗病毒疫苗接种策略预防或治疗宫颈癌创造了独特机会。在预防HPV感染和治疗已存在的HPV相关疾病的临床试验中，已经研究了几种策略。使用含有病毒样颗粒（VLP）的预防性疫苗的临床试验显示出良好的疫苗效力，预计在未来五年内可能会有预防性疫苗上市。但是，该领域的临床前研究仍在继续，以解决诸如在服务不足的第三世界人群中疫苗接种成本等问题。大多数使用旨在预防已存在的HPV相关病变或癌症进展的治疗药物的临床试验显示，在根除人类已形成的肿瘤方面疗效有限，这可能是因为研究的是癌症晚期患者，他们的免疫功能往往较低。未来治疗药物的临床试验趋势将针对早期癌症或癌前病变患者进行研究，以预防浸润性宫颈癌。与此同时，该领域的临床前研究仍在继续，包括对肽或蛋白质疫苗接种的进一步探索，以及在基于DNA的疫苗或病毒载体中递送HPV抗原。鉴于宫颈癌是由人乳头瘤病毒引起的，治疗性疫苗治疗现有病变以及预防性疫苗预防病毒持续感染的前景广阔，可能在不久的将来得以实施。临床管理方面的影响可能包括，对于预防性疫苗而言，巴氏涂片筛查的频率将大幅降低；对于治疗性疫苗而言，可为患有已存在的HPV相关病变的女性提供侵入性较小且不会毁容的治疗选择。预防性和治疗性疫苗接种方案的实施可能会显著降低医疗保健成本，并降低全球宫颈癌发病率。
