人乳头瘤病毒疫苗防治宫颈癌研究的新进展

宫颈癌的发病率在女性恶性肿瘤居第二位,人乳头状瘤病毒(HPV)感染已被证实为宫颈癌发生的主要因素,采用HPV疫苗防治HPV感染和宫颈癌是最根本的病因治疗方法,其中HPV疫苗分为预防性疫苗和治疗性疫苗两大类,本文综述了近几年关于HPV疫苗的研究成果.     

宫颈癌与hpv关系的研究进展

宫颈癌是1种常见的女性恶性肿瘤。目前我国的宫颈癌发病呈总体下降但年轻患者增加的趋势。分子流行病学研究已经证实：人乳头瘤病毒（HPV）的感染与宫颈癌有着十分密切的关系。宫颈癌的筛查可以降低宫颈癌发生的危险,却不能阻止HPV的感染。目前对HPV的感染尚无确切治疗方法,但是已有研究采用HPV的疫苗来预防和治疗该病毒的感染,以此来预防宫颈癌的发生。有大规模研究证实,应用HPV疫苗的获益大于风险。因此,研究HPV和宫颈癌的关系对于宫颈癌的预防及治疗都有重要意义。     

高危型HPV相关宫颈癌发生及其预防和治疗疫苗

高危型HPV感染,是宫颈癌发生的重要因素.高危型HPV E6,E7癌基因的过最表达是诱发宫颈癌的关键.针对高危型HPV感染的生物学过程,可以设计两种疫苗:预防和治疗高危型HPV相关宫颈癌,前者称预防疫苗,后者称治疗疫苗.特别是针对宫颈癌的以E6.E7为靶子的重组病毒载体治疗疫苗,研究较深入,已经进入临床试验.     

疫苗的“辩论”

7年来,被寄予厚望的HPV疫苗已在全球一百多个国家获得批准,然而在大多数国家它的应用并不普遍。印度是第一个开展人体试验的发展中国家,遗憾的是,在印度的疫苗试验却出现了较大的意外。人类乳头瘤病毒（HPV）感染被认为是诱发宫颈癌的重要因素,由于HPV疫苗能防止HPV感染,因此也被称为宫颈癌疫苗。     

宫颈癌那些事儿

目前,随着人乳头瘤病毒（HPV）二价疫苗和四价疫苗在国内的上市,HPV感染的相关话题简直就是沸沸扬扬、人人关注。HPV疫苗上市之所以能够在社会上引起这么大的轰动和反响是因为HPV是导致宫颈癌的元凶。因此广大女性朋友们不仅谈宫颈癌色变,提起HPV也非常恐慌。那么,是否感染了HPV肯定就会得宫颈癌呢？怎样才能知道自己是不是得了宫颈癌？     

预防性 HPV 疫苗的临床应用进展及思考

宫颈癌是女性生殖系统最常见的恶性肿瘤,并且高危型人乳头瘤病毒（human papillomavirus, HPV）持续感染与宫颈癌的密切关系已经得到流行病学及临床研究证实。因此,HPV 疫苗在预防 HPV 持续感染及宫颈相关病变等方面备受瞩目。本文对目前美国 FDA 批准上市的3种预防性疫苗的临床应用进展进行综述,同时列举出一些尚存在争议的问题,旨在引起人们的重视及共同思考。     

人乳头状瘤病毒（HPV）疫苗的研究进展

人乳头状瘤病毒(human papillomavirus,HPV)感染是宫颈癌的主要病因.清除HPV感染和阻断由HPV感染所引发的宫颈癌前病变的进展尚缺乏理想的方法.目前,国际上已有20多种HPV相关疫苗已进入动物和临床试验阶段,主要分为预防性疫苗和治疗性疫苗,主要制剂形式是蛋白质、核酸.动物实验和临床试验结果显示HPV疫苗将在预防HPV感染及治疗由感染所引起的相关疾病方面有重要作用.     

人乳头瘤病毒治疗性疫苗的研究进展

人乳头瘤病毒(HPV)持续感染是宫颈上皮内瘤变和宫颈癌发生的必要因素.以治疗HPV感染为出发点研制有效的治疗性疫苗是防治宫颈癌的新策略.近年来,治疗性HPV疫苗的研制与试验已取得了巨大的进步,载体的选择、佐剂的使用、融合和嵌合蛋白的合成被广泛应用于研究中,以增强疫苗免疫原性、加强接种安全性、减少不良反应等.临床试验结果令人鼓舞,各类疫苗能诱导特异性免疫应答,且具有良好的耐受性;但如何取得进一步的成功依然需要大量的研究.此外,HPV病毒种类繁多,如何扩大疫苗的作用范围及减少免疫逃逸也是研究的重点.     

宫颈癌的筛查及临床诊治

宫颈癌是女性的第二杀手，是HPV感染的疾病。有合理的筛查方案，两种HPV疫苗已经用于临床．辅助检查方法多，手术和化放疗效果肯定。文章主要就以上进行论述。     

宫颈癌的病因及宫颈癌疫苗现状

宫颈癌是继乳腺癌后第二位的女性常见恶性肿瘤，2016年世界卫生组织报道:每年全球有超过47万新发的宫颈癌病例，作为发展中国家的中国约占其中的28%，并预计直至2025年，亚洲的宫颈癌发病例将上升约40%。据资料表明:全世界大约90%以上的宫颈癌是由９种或者9种以上的高危型HPV所导致的。尽管目前针对宫颈癌的病因研究及癌前筛查已经得到较好的普及和发展，但随着科技及医疗的不断发展，宫颈癌的病因治疗以及预防仍是全球医疗的热点问题。本文对于宫颈癌的发病因素及宫颈癌疫苗的发展现状作一综述，以便临床参考，提高宫颈癌的检出率，降低其发病率。     

Vaccines against human papillomavirus and cervical cancer: promises and challenges

Cervical cancer and precancerous lesions of the genital tract are major threats to the health of women worldwide. The introduction of screening tests to detect cervical cancer precursor lesions has reduced cervical cancer rates in the developed world, but not in developing countries. Human papillomavirus (HPV) is the primary etiologic agent of cervical cancer and dysplasia. Thus, cervical cancer and other HPV-associated malignancies might be prevented or treated by HPV vaccines. Two vaccine strategies have been developed. First, prevention of HPV infection through induction of capsid-specific neutralizing antibodies has been studied in clinical trials. However, because the capsid proteins are not expressed at detectable levels by infected basal keratinocytes or in HPV-transformed cells, a second approach of developing therapeutic vaccines by targeting nonstructural early viral antigens has also been developed. Because two HPV oncogenic proteins, E6 and E7, are critical to the induction and maintenance of cellular transformation and are coexpressed in the majority of HPV-containing carcinomas, most therapeutic vaccines target one or both of these gene products. A variety of approaches is being tested in therapeutic vaccine clinical trials, whereby E6 and/or E7 are administered in live vectors, as peptides or protein, in nucleic acid form, or in cell-based vaccines. The paradigm of preventing HPV infection through vaccination has been tested, and two vaccines are currently in phase III clinical trials. However, current therapeutic vaccine trials are less mature with respect to disease clearance. A number of approaches have shown significant therapeutic benefit in preclinical papillomavirus models and await testing in patient populations to determine the most effective curative strategy.     

Review of the Cervical Cancer Disease Burden in Mainland China

Human papillomavirus (HPV) infection is a common sexually transmitted infection (STI) worldwide. HPVmay cause several reproductive tract diseases and cervical cancer is the most serious health problem due topersistent high risk HPV infection. Although cervical cancer showed a declining trend over the past three decadesin China, it remains a major health problem in Chinese women especially women living in rural China. Thedisease burden is believed to be underestimated given the relatively high HPV prevalence shown in recent studies.To date, prophylactic vaccination as a primary prevention of cervical cancer are available in many countries andregions of the world; yet, they are not yet accessible in mainland China. Before introduction of HPV vaccines,screening remains the predominant method of prevention. Selected population based screening sites are availablein every province of China, yet, an organized screening program operating nationwide still does not exist. Abetter understanding of the disease burden is likely to help develop a comprehensive intervention policy forfuture management of cervical cancer in China. It is important to review the disease burden of cervical cancerand the current status of cervical cancer screening in mainland China.     

Human papillomavirus vaccines versus cervical cancer screening

Prophylactic vaccination with human papillomavirus (HPV) virus-like particle (VLP) vaccines against HPV 16 and HPV 18, which are the cause of 70% or more of cervical cancers in women, has transformed our prospects for reducing the incidence of this disease on a global scale. HPV VLP vaccines are immunogenic, well tolerated and show remarkable efficacy, achieving >98% protection in randomised clinical trials against the obligate precursor lesions cervical intraepithelial neoplasia grade 2/3 (CIN2/3) and adenocarcinoma in situ. The implementation of these vaccines as a public health intervention is, however, complex. Cervical cancer screening can be a highly effective secondary intervention, but in the developing world these programmes are either not available or are ineffective. HPV vaccination represents the most effective intervention in that scenario. In countries with successful well-organised cervical cancer screening programmes, such as the UK, the cost-effectiveness of vaccination as opposed to screening is a major factor. Screening will have to continue, as only two of the 15 oncogenic HPV types are in the vaccines and for two to three decades at least unvaccinated sexually active women will remain at risk for the disease. However, if both vaccination and screening are combined then the virtual elimination of cervical cancer and the other HPV 16 and 18-associated cancers is possible.     

Human papillomavirus vaccines in HIV-positive men and women

PURPOSE OF REVIEW: Individuals with HIV are at greater risk of human papillomavirus-related cancers. This report will assess the potential and limitations of vaccines against human papillomavirus in HIV-positive individuals. RECENT FINDINGS: A worldwide meta-analysis of published data established the under-representation of HPV16, and increased prevalence of multiple-type human papillomavirus infections in HIV-positive women. Associations between HIV-related immunodepression, the progression of human papillomavirus infection to cervical lesions, and an increased risk of cervical cancer in women with HIV have also been shown. An increased incidence of human papillomavirus infection in anal and vulvar/vaginal neoplasia has been reported in individuals with HIV. A prophylactic vaccine against HPV6, 11, 16 and 18 has been licensed, and one against HPV16 and 18 is under evaluation. Both have shown efficacy against persistent infection, as well as related human papillomavirus cervical lesions for up to 5 years. Preliminary results have also been reported on therapeutic vaccines, notably for the treatment of cervical intraepithelial neoplasia grades 2 and 3. SUMMARY: The safety and efficacy of human papillomavirus vaccines in individuals with HIV need to be assessed to prevent cervical cancer in current and future generations. Screening for human papillomavirus-related cancer among HIV patients should be undertaken.     

Advances in dendritic-cell-based therapeutic vaccines for cervical cancer

Cervical cancer is the second leading cause of cancer death among women worldwide and remains an important health problem for women, especially in underserved and minority groups in industrially developed nations. Although radical surgery and radiotherapy represent effective modalities of treatment for invasive cervical cancer, up to 35% of these patients overall will develop recurrent/metastatic disease for which treatment results remain poor. Novel therapeutic strategies that are effective in reducing the risk of recurrence/metastatic disease are still needed desperately. Human papillomavirus (HPV) infection represents the most important risk factor for the development of cervical dysplasia and cervical cancer. Since HPVE6 and E7 oncoproteins are constantly expressed in these lesions, these foreign proteins represent ideal tumor-specific target antigens for immunotherapy of cervical cancer. Recently, the recognition of dendritic cells (DC) as powerful antigen-presenting cells, capable of inducing primary T-cell responses in vitro and in vivo, has generated widespread interest in DC-based immunotherapy of several human malignancies. This review summarizes the therapeutic clinical trials and the different preclinical research strategies that are under investigation, with a particular emphasis on the use of autologous DC-pulsed HPV16 or 18 E7 oncoproteins as therapeutic vaccines against cervical cancer.     

Integrating novel primary- and secondary-prevention strategies: the next challenge for cervical cancer control

The advent of prophylactic vaccines against human papillomavirus (HPV) infection, the cause of cervical cancer, and of new molecular methods to screen for this disease have become key developments in cancer control in the last 5 years. Although Pap cytology has had a significant history as a key method for cervical cancer screening, not all countries have benefited from this technology or have been able to implement the necessary public health steps to manage and treat the precancerous lesions that are detected by the Pap test. Testing of cervical exfoliated cells for DNA of oncogenic HPV types has been proven to be more accurate than Pap cytology. The latter test's high specificity makes it an ideal technique to triage women who are found to be HPV positive via a primary screen. HPV testing followed by Pap testing only for HPV-positive women is a promising strategy for screening women in the post-vaccination era.     

Human papillomavirus vaccine as a new way of preventing cervical cancer: a dream or the future?

Cervical cancer is the major cause of death in women of reproductive age in parts of the developing world. Thanks to the effectiveness of national screening programs, the incidence and mortality rates for cervical cancer have declined dramatically in developed countries. According to many researchers, human papillomavirus (HPV) infection has an important role in the development of cervical neoplasm. The effects of HPV infection on the oncogenesis of cervical carcinoma can be explained to a large degree by the regulation and function of the two viral oncogenes, E6 and E7. About 25 of >80 types infect the genital tract. HPV types are stratified into low, intermediate- and high-risk categories. Today, vaccines are available against many serious human pathogens. It is accepted worldwide that cervical carcinoma is a consequence of infection with HPV viruses. Therefore it is reasonable to assume that vaccine that prevents infection will reduce the incidence of cervical cancer. Virus-like particles are empty viral capsids, and are the leading candidate vaccines for the treatment or prevention of cervical cancer in humans. The HPV type 16 (HPV16) L1 virus-like particle vaccines have been shown to be generally well tolerated and they generate high levels of antibodies against HPV16. Since approximately 50% of cervical cancers are associated with HPV16 infection, the administration of this type of vaccine to young women could reduce the incidence of HPV16 infection, which is related to cervical dysplasia and cervical neoplasm. Vaccination against HPV infection could reduce the risk of infection and, most importantly, decrease the incidence of cervical cancer. A vaccine for cervical cancer is not a dream in the far future, it is happening today.     

Current status of cervical cancer and HPV infection in Korea

Cervical cancer is an important cause of cancer-related deaths in women in developing countries. In Korea, cervical cancer is the third leading cancer among females and is fifth highest in mortality. The persistent oncogenic human papillomavirus (HPV) infections are the greatest risk of developing cervical intraepithelial neoplasia and invasive cancer. The overall prevalence of HPV was 10.4% in Korea and strong risk factors for HPV infection included a young age at sexual debut. The National Cancer Screening Program, which includes cervical cancer screening, has the following principles: the main screening tool is the Papanicolaou test conducted by gynecologists, which targets all women age 30 and over, and which is done every 2 years. HPV DNA tests have not yet been permitted as a screening test for cervical cancer in Korea; however, these are conducted along with a Pap test for screening cervical cancer in the clinic. The use of prophylactic HPV vaccine has been accepted in Korea; The Korean Society of Gynecologic Oncology and Colposcopy''s recommendation for routine vaccination is for females aged 15-17 years with a catch-up vaccination recommended for females aged 18-26 years who have not been previously vaccinated. However, many people in Korea are not familiar with the HPV vaccine. Therefore, it is necessary to improve awareness for the disease and HPV vaccination and to establish the effective strategies to obtain funding for HPV vaccination. In the future, cervical cancer is expected to disappear throughout the world, including the Asia Pacific region, through a combination of vaccination and qualified screening programs for cervical cancer.