子宫颈高级别上皮内病变治疗后HPV疫苗预防复发的研究进展

由于各种原因,宫颈高级别鳞状上皮内病变(HSIL)锥切治疗后病变持续/复发率仍较高,且进展为宫颈癌的风险明显高于普通人群。除治疗后严密随访外,如何减少宫颈HSIL治疗后的复发,成为一个临床关注的问题。预防性HPV疫苗对其相关型生殖道癌前病变和癌均有很好的预防效果,已广泛应用于适龄女性。最近的研究显示,宫颈HSIL治疗后患者接种预防性HPV疫苗也可显著降低病变的持续/复发率,提示治疗后接种HPV疫苗仍可获益,从而减少再次治疗相关的并发症,这一观点可能影响宫颈HSIL治疗后的管理,扩大预防性HPV疫苗的应用范围。因此,本文对宫颈HSIL治疗后接种HPV疫苗对病变复发影响的相关临床研究进展进行综述。     

人乳头瘤病毒疫苗接种及研究现状

人乳头瘤病毒(HPV)是最常见的性传播病毒。高危型HPV持续感染可以诱发生殖器官的癌前病变和癌症。减少HPV感染,预防宫颈癌是HPV疫苗研制的出发点之一。接种预防性HPV疫苗可以减少HPV感染相关的疾病发生率,具有良好的公共卫生意义和成本效应。但治疗性HPV疫苗目前研究进展缓慢,缺乏大规模临床Ⅰ试验结果。     

人乳头瘤病毒疫苗临床应用中国专家共识(2021年版)解读

<正>人乳头瘤病毒(human papilloma virus,HPV)疫苗接种是防控HPV感染相关疾病的一级预防措施。2021年，中华医学会妇科肿瘤学分会与中国优生科学协会阴道镜和子宫颈病理学分会(CSCCP)组织专家联合制定了《人乳头瘤病毒疫苗临床应用中国专家共识》[1](简称HPV临床应用共识)。该共识涵盖了HPV及疫苗介绍、HPV疫苗接种人群的选择和不同推荐级别和接种时机(尤其高危、特殊人群)、不良反应(AR)和不良事件(AE)及其处理、注意事项等多方面内容，本文对备受关注点的热点进行解读和背景分析。     

HPV治疗性疫苗研究现状

<正>宫颈癌是目前我国仅次于乳腺癌的女性常见恶性肿瘤,每年约有3万妇女死于宫颈癌。高危型人乳头瘤病毒(human papilloma virus,HPV)的持续感染是引发宫颈癌的最主要原因,HPV感染最多的高危型别为16、18、52、58、31,其中尤以HPV16、18感染率最高。如今,HPV疫苗作为防治宫颈癌及HPV相关疾病的重要手段被广泛关注。预防性的HPV二价疫苗     

宫颈癌HPV预防性疫苗的研究进展

人乳头瘤病毒（HPV）感染是常见的性传播疾病之一。高危人乳头瘤病毒（hrHPV）持续感染是宫颈癌前病变及宫颈癌的主要危险因素。HPV16和HPV18型导致全球大约70%的宫颈癌。宫颈癌普查可减少宫颈癌发生的危险,但不能阻止HPV的感染。很多报道表明,有效的HPV疫苗可以减少HPV相关的宫颈癌、生殖道疣状物的发病率和死亡率。因此,为了有效预防这类疾病,全世界开展了HPV预防性疫苗的研究。目前临床应用的HPV疫苗有HPV 2价疫苗、4价疫苗及9价疫苗,它们可以有效预防相应HPV类型的感染,从而大量减少与此相关的宫颈病变及宫颈癌的发病率和死亡率。本文就HPV、宫颈癌及这3类HPV疫苗的免疫原性、接种剂量的数量和临床应用进行综述。     

宫颈癌HPV预防性疫苗的研究进展

人乳头瘤病毒(HPV)感染是常见的性传播疾病之一。高危人乳头瘤病毒(hr HPV)持续感染是宫颈癌前病变及宫颈癌的主要危险因素。HPV16和HPV18型导致全球大约70%的宫颈癌。宫颈癌普查可减少宫颈癌发生的危险,但不能阻止HPV的感染。很多报道表明,有效的HPV疫苗可以减少HPV相关的宫颈癌、生殖道疣状物的发病率和死亡率。因此,为了有效预防这类疾病,全世界开展了HPV预防性疫苗的研究。目前临床应用的HPV疫苗有HPV 2价疫苗、4价疫苗及9价疫苗,它们可以有效预防相应HPV类型的感染,从而大量减少与此相关的宫颈病变及宫颈癌的发病率和死亡率。本文就HPV、宫颈癌及这3类HPV疫苗的免疫原性、接种剂量的数量和临床应用进行综述。     

外阴癌和阴道癌早期诊断及预防

虽然外阴癌、阴道癌发病率不高,但年轻女性发病比例上升。高危型人乳头瘤病毒(HPV)感染是外阴癌、阴道癌的重要致病因素。常规妇科检查时,尤其是对HPV高危型感染的妇女,应注意阴道、外阴的检查,以期早期发现外阴、阴道癌。年轻女性接种HPV疫苗可从病因上预防相当一部分的外阴癌和阴道癌。     

新疆乌鲁木齐市2589例宫颈人乳头瘤病毒感染现况分析

目的 分析新疆乌鲁木齐市2 589例女性人乳头瘤病毒（human papilloma virus, HPV）感染分布特点。方法 收集2020年3月至2022年3月在新疆医科大学第一附属医院健康管理中心体检检测出HPV感染者,分析HPV感染情况、年龄分布、亚型分布特点。结果 20 778例中18 189例（87.54%）HPV阴性,105例（0.51%）接种HPV疫苗,2 589例（12.46%）HPV阳性,0例（0.00%）接种HPV疫苗。≤25岁年龄段中HPV阳性占比最高,46～55岁女性中阳性占比最少。HPV单一基因型感染2 136例（82.50%）,HPV多重感染453例（17.50%%）。不同年龄段HPV单一感染和多重感染差异有统计学意义（P <0.05）。不同年龄段的感染阳性率均呈倒“U”型。高危型感染以HPV52(17.11%)、HPV16(16.03%)为主,且明显高于其他亚型,中危型感染以HPV 53(12.40%)、HPV66(7.49%)为主,低危型感染以HPV6(1.43%)、HPV11(1.20%)、HPV81(7.30%)为主。结论 新疆乌鲁木齐女性人群...     

人乳头瘤病毒与妊娠结局的相关性

人乳头瘤病毒(human papilloma virus,HPV)是生殖道感染最常见的病毒之一,HPV尤其是高危型HPV的反复感染易转变为宫颈上皮内瘤变,甚至会诱发宫颈、肛门及口咽腔的恶性肿瘤。育龄期男性与女性是HPV感染的多发群体,有文献报道,HPV感染可能对生殖健康与妊娠产生不利影响。结合近年发表的国内外文献对HPV感染与妊娠结局相关问题,从HPV妊娠期易感性、HPV感染对异常妊娠的影响、HPV感染与分娩方式及新生儿结局、HPV感染对辅助生殖技术妊娠成功率及妊娠结局的影响、接种HPV疫苗对妊娠的影响几方面进行综述。     

我国加速消除子宫颈癌的挑战与机遇

子宫颈癌是全球女性常见的恶性肿瘤。2018年, WHO总干事向全球发出了消除子宫颈癌的动员令。我国的子宫颈癌人群防治工作累积了大量的实践经验, 并取得一定成效。面对2030年"90%-70%-90%"的阶段性目标, 我国仍有不同程度的挑战和机遇。人乳头状瘤病毒(HPV)疫苗在国内得以应用, 部分省市已开展适龄人群接种, 90%适龄女性接种疫苗的阶段性目标的实现较为乐观, 应密切关注国际上HPV疫苗接种的研究进展;子宫颈癌人群筛查技术已取得突破性进展, 但我国存在人口基数大、资源不足等困难, 70%适龄女性接受高效检测方法筛查的目标存在较大困难, 应尽早推广应用新技术, 快速提高筛查服务能力及其均质化;我国子宫颈病变的治疗水平不断进步, 且随着总体经济发展、基本医疗保险高覆盖、医保政策优化等, 预计90%确诊子宫颈病变的妇女得到治疗的阶段性目标能够实现, 目前应开展全国性治疗数据的收集。我国实现消除子宫颈癌的战略目标任重而道远。     

Human Papillomavirus: The Usefulness of Risk Factors in Determining Who Should Get Vaccinated

Vaccination against human papillomavirus (HPV) promises to dramatically decrease the incidence of HPV-related diseases, including cervical cancer. Although this vaccine is recommended by the Advisory Committee on Immunization Practices and The American College of Obstetricians and Gynecologists for all age-eligible women, challenges related to the vaccine’s high cost and the difficulty in reaching some patients for vaccination may make implementation of this recommendation difficult. As an alternative strategy, some may consider targeting HPV vaccines to specific patients based on their risk for HPV infection or HPV-related disease. This article reviews what is known about risk factors for HPV, and discusses why using risk factors as the basis for targeting HPV vaccination is unlikely to be a viable vaccination strategy.Key words: Human papillomavirus, Risk factors, Vaccine, Vaccination strategiesIn June 2006, the US Food and Drug Administration licensed the first vaccine against human papillomavirus (HPV) for use in the United States.¹ This vaccine promises to dramatically reduce the incidence of HPV-related diseases such as cervical dysplasia, cervical and other anogenital cancers, and genital warts. The Advisory Committee on Immunization Practices (ACIP) recommends that all 11- to 12-year-old girls be vaccinated against HPV routinely, with comprehensive catch-up vaccination suggested for girls and women ages 13 to 26 who have not yet received the vaccine and vaccination allowable for girls as young as age 9 who are perceived to be at high risk.² In keeping with this comprehensive approach, The American College of Obstetricians and Gynecologists (ACOG) also recommends vaccination of girls and women within the eligible age range.³Although a comprehensive vaccination strategy would maximize the vaccine’s impact on HPV-related disease, implementation of this type of strategy may prove difficult as providers, patients, and parents of patients struggle to overcome challenges related to the vaccine’s high cost, and because of the logistical challenges of getting certain populations of patients vaccinated. Because of these obstacles, an alternative vaccination strategy that some might consider is to vaccinate only certain subpopulations of women based on their risk of HPV infection or HPV-related disease. A targeted approach such as this has been suggested by the American Cancer Society which, for women ages 19 to 26, recommends that HPV vaccination occur in the context of a discussion with the medical provider to weigh the likelihood of previous HPV exposure with the vaccine’s financial cost and the potential benefits of vaccination.⁴ This article reviews what is known about risk factors for HPV infection and disease, and discusses some of the pitfalls of using risk factors as a basis for targeted HPV vaccination approaches.     

Why consider human papillomavirus vaccination in older women?

Preventive human papillomavirus (HPV) L1 vaccines are safe and efficient to prevent infection and lesions of vaccine- specific HPV types in women from 15 to 26 years, but also in older age groups. Clearly, public health funds are to be spent to organize programs for vaccination of young adolescents. Immunobridging studies and clinical trials have shown that HPV vaccines generate significantly higher plasma antibodies than following natural infections in women up to 55 years and prevent up to 90.5% (95% CI 73.7-97.5) vaccine-specific HPV infections and lesions in women aged 24-45 years who are HPV DNA-negative at the time of vaccination. However, data from clinical trials with HPV L1 vaccines in older women (older than 25 years) are still scarce compared to the amount of evidence from trials in women younger than 26 years. Information from large population-based studies indicates that older women remain at risk of infection by high-risk HPV and the risk of persistent high-risk HPV infection is significantly higher than in young women, leading to a higher risk of progressing disease and carcinoma. The natural history of HPV infection remains enigmatic as we do not know if the immune mechanisms that clear the HPV infection offer prolonged protection. On the contrary, some data indicate that seroconversion after a natural infection only partially protects against re-infection. Given the large proportions of adult men and women that change sexual partners, the protective effects of HPV L1 vaccines may offer an extra benefit against HPV-related genital diseases within a much shorter time period than after vaccination of prepubertal adolescents.     

Human papillomavirus vaccination in the United Kingdom: what about boys?

In September 2008 the UK Department of Health initiated a human papillomavirus (HPV) immunisation programme for girls aged 12-13 for prevention of cervical cancer, which is most often caused by two HPV types. An important question, yet to be addressed, is whether boys should also be vaccinated. Men also get HPV and transmit it sexually, not just women. Certain HPV types are associated with genital warts, which have significant morbidity, and with difficult to treat non-cervical malignancies, including vulval, penile, anal and oro-pharyngeal cancer, which are best prevented through vaccination. Moreover, increased persistence of HPV infection is associated with HIV infection. A review of the literature and evidence from modelling suggest that vaccinating boys would increase vaccination impact and may be necessary to achieve herd immunity targets. Excluding boys sends the wrong message that girls and women alone are responsible for sexual health. Although protective efficacy of the vaccine in men has not yet been fully established, the rationale for vaccinating boys as well as girls at an early age is strong, assuming efficacy is established. Meanwhile, provision of the quadrivalent vaccine should become UK policy, in order to include protection against genital warts, the argument for which is strengthened if boys are also vaccinated.     

Eligibility and willingness of first-year students entering university to participate in a HPV vaccination catch-up program

Objectives

In France, human papillomavirus (HPV) vaccine is routinely recommended for 14-year-old girls; a catch-up vaccination should be offered to girls and women 15–23 years of age before the first time they have sex or within the first year after sexual activity begins. The aim of the present study was to examine the eligibility and willingness of first-year college students of Toulouse University (France) to participate in a HPV vaccination catch-up program, and to estimate their knowledge of HPV vaccination and cervical cancer screening.

Study design

The study was conducted from January to April 2008 simultaneously at the three university medical centres (Science, Literature-Psychology, Law-Social Sciences). Female students entering the University were asked to complete an anonymous questionnaire at the time of their preventive medical visit. The questionnaire included questions on demographics, knowledge about HPV vaccination, sexual behaviour, and willingness to participate in the French vaccination program.

Results

In total, 606 women from the 3 colleges were included. The response rate of the questionnaire was 93.1%. The median age of participants was 19 and 8.3% of them had already been vaccinated. Of the respondents, 67.2% were sexually experienced and 25.3% of sexually experienced students had their first intercourse less than 1 year prior. Knowledge of HPV infections, associated diseases, and prevention was limited, a finding that indicates the need to pursue educational campaigns. Among respondents, 42.7% were eligible for catch-up vaccination, and 64.1% of them were willing to be vaccinated. We did not observe significant differences among the three colleges.

Conclusions

First-year college preventive consultation is an opportunity to vaccinate near 43% of women according to French recommendations. Improved education about HPV-related diseases and their prevention is needed.     

HPV infection in etiology of uterine cervix cancer

Uterine cervical cancer may be the direct result of persistent HPV infection. The DNA analysis shows over 200 HPV types. The natural history of uterine cervix cancer is a constantly progressing process, from low pathology changes, through medium to major pathology changes, including microinvasion and invasive carcinoma. The population studies show that over 20% of women at the moment of examination is infected with HPV. The study of cervical cancer tissue revealed the HPV in the DNA, whereas the serological study revealed the presence of specific antibodies to HPV capsid antigens in most women (in USA the number amounts up to 70%). The serological conversion after HPV infection is not a common process. Therefore, the naturally infected women, still do not have enough antibodies and they are at the risk of infection, just as seronegative women. The vaccination of women between the ages of 15 and 25, causes the increase of the number of antibodies, several times higher than in the case of naturally acquired ones. The positive results of HPV examination is not a contraindication to vaccination. However, in case of vaccinated women, the negative test for 14 oncogenic HPV types has an overwhelmingly negative predictive value. Independent of the presence or absence of HPV infection, it is essential to continue cytological. The vaccination does not protect patients from all oncogenic HPV types. Cytological screening enables doctors to recognize cervical pathology at the early stage and introduce a proper treatment.     

Human papillomavirus infection and cervical disease in human immunodeficiency virus-1-infected women

OBJECTIVE: To report on the natural history of high-risk human papillomavirus (HPV) infection and cervical disease in human immunodeficiency virus (HIV)-1-infected women living in Cape Town, South Africa. METHODS: This was a prospective study of 400 untreated, HIV-1-infected women who underwent high-risk HPV DNA testing, cytology, colposcopy, histology, and CD4 count testing every 6 months for 36 months. Human immunodeficiency virus viral loads and HPV type distribution were determined at entry and after 18 months. RESULTS: Sixty-eight percent of the women were high-risk HPV DNA positive at entry, 35% had a cytologic diagnosis of low-grade squamous intraepithelial lesion (LSIL), and 13% had high-grade squamous intraepithelial lesion (HSIL). There were no cancers. Abnormal cytology and high-risk HPV positivity were strongly correlated with low CD4 counts and high HIV viral loads. The most prevalent types of HPV were HPV-16, -52, -53, -35, and -18. Incident high-risk HPV infection occurred in 22%, and of those infected with high-risk HPV, 94% of infections persisted over an 18-month period, and 6% cleared their infections. Cytologic progression to SIL from normal/atypical squamous cells of undetermined significance cytology occurred in 17% of cases, but only 4% of cases of LSIL progressed to HSIL. CONCLUSION: There is a high level of high-risk HPV infection in HIV-1 infected women, but progression to HSIL over 36 months occurred in the minority of cases. We recommend an initial colposcopy for an abnormal test, and if no high-grade lesion is identified, triennial screening would be appropriate. Human papillomavirus type 16 was the commonest, and HPV-18 was the fifth commonest, suggesting that vaccination against these two types would have a significant effect. LEVEL OF EVIDENCE: II.     

Cervical Adenocarcinoma in Situ: Update and Management

Adenocarcinoma in situ (AIS) of the uterine cervix is caused by infection with high-risk human papillomavirus and is the recognized precursor of invasive adenocarcinoma of the cervix. Because most AIS lesions are caused by HPV 16/18 infection, prophylactic HPV vaccination is an important step toward prevention of AIS, potentially reducing the incidence of invasive adenocarcinoma. Nonetheless, at the moment the incidence of AIS and invasive adenocarcinoma continues to increase, especially among young women when fertility preservation is an issue. Both diagnosis and treatment of AIS is challenging, because AIS lesions frequently extend into the endocervical canal, making detection and complete excision difficult. Hysterectomy remains the standard treatment for AIS. Selected patients, who wish to preserve fertility, with clear margins and negative ECC after initial conization are potential candidates for conservative treatment. If margins are involved after initial conization or ECC results are positive, the risk of residual or recurrent AIS and invasive adenocarcinoma of the cervix is considerably high. In these women, repeat surgery should be performed. For women, who do not undergo hysterectomy, long-term follow-up is recommended.     

Understanding Human Papillomavirus Vaccination Intentions: Comparative Utility of the Theory of Reasoned Action and the Theory of Planned Behavior in Vaccine Target Age Women and Men

IntroductionHuman papillomavirus (HPV) is an exceedingly prevalent sexually transmitted infection with serious medical, sexual, and relationship consequences. HPV vaccine protection is available but vaccine uptake is very inconsistent.AimsThis research applies two major theories of health behavior uptake, the Theory of Reasoned Action and the Theory of Planned Behavior, in an effort to understand intentions to receive HPV vaccine among vaccine target age women and men. The Theory of Reasoned Action asserts that attitudes toward HPV vaccination and perceptions of social support for HPV vaccination are the determinants of intentions to be vaccinated, whereas the Theory of Planned Behavior holds that attitudes toward vaccination, perceptions of social support for vaccination, and perceived ability to get vaccinated are the determinants of intentions to be vaccinated.MethodsCanadian university men (N = 118) and women (N = 146) in the HPV vaccine target age range took part in this correlational study online.Main Outcome MeasuresParticipants completed standard measures of attitudes toward HPV vaccination, perceptions of social support for vaccination, perceived ability to get vaccinated, beliefs about vaccination, and intentions to be vaccinated in the coming semester.ResultsFindings confirmed the propositions of the Theory of Reasoned Action and indicated that attitudes toward undergoing HPV vaccination and perceptions of social support for undergoing HPV vaccination contributed uniquely to the prediction of women's (R² = 0.53) and men's (R² = 0.44) intentions to be vaccinated in the coming semester.ConclusionClinical and public health education should focus on strengthening attitudes and perceptions of social support for HPV vaccination, and on the basic beliefs that appear to underlie attitudes and perceptions of social support for HPV vaccination, in efforts to promote HPV vaccine uptake. Fisher WA, Kohut T, Salisbury CMA, and Salvadori MI. Understanding human papillomavirus vaccination intentions: Comparative utility of the Theory of Reasoned Action and the Theory of Planned Behavior in vaccine target age women and men. J Sex Med 2013;10:2455–2464.     

持续性高危型人乳头瘤病毒感染的处理

持续性高危型人乳头瘤病毒（HPV）感染是子宫颈癌及其癌前病变发生的必要条件；其定义尚有分歧，因此感染率并不确切。尽管子宫颈癌筛查指南日趋完善，但关于持续性高危型HPV感染的处理举措并无系统阐述。对于无组织学病变的持续性高危型HPV感染患者，是否治疗、如何治疗亦是临床实践中的难题。文章回顾已发表文献就其定义、感染率、处理措施及预防进行阐述。     

A National Survey of Canadian Adults on HPV: Knowledge,Attitudes, and Barriers to the HPV Vaccine

ObjectiveIdentifying human papillomavirus (HPV) vaccination motivators and barriers among adults could lead to new approaches to improve HPV vaccination rates in non-pediatric populations. This Canadian survey aimed to assess current knowledge of, attitudes towards, and barriers to the HPV vaccine among the general public.MethodsAn online panel was used to survey HPV unvaccinated women (n = 802) and vaccinated women (n = 250) 18 to 45 years old, as well as 18- to 26-year-old men (n = 200), in May and June 2016. A 16-item questionnaire collected data on sociodemographic factors, health-seeking behaviours, knowledge of HPV infection and its consequences, and the HPV vaccine. Data were stratified by sex and by vaccination status among women.ResultsThe majority of individuals somewhat or strongly agreed that vaccination is an important aspect of disease prevention (vaccinated women, 93%; unvaccinated women, 85%; and men, 59%). However, a high proportion of patients were concerned about vaccine safety (vaccinated women, 26%; unvaccinated women, 40%; and men, 36%). Moreover, 58% to 61% of participants were generally cautious about taking any vaccine. The number one reported barrier to vaccination was not having a recommendation from a doctor (38%). Cost was seen as a barrier by only 18% to 20% of participants.ConclusionCanadian participants show a broad diversity in HPV knowledge and regarding barriers to vaccination. The youngest populations (vaccinated women and men) showed higher levels of knowledge regarding HPV.