尖锐湿疣的特点及治疗规范(Copy)

尖锐湿疣的特点及治疗规范 概述 尖锐湿疣（CA）又称生殖器疣、性病疣，是由HPV引起的生殖器、会阴和肛门等部位的良性表皮肿瘤 属五种上报STD之一 STD病种的变化： 细菌性STD  病毒性STD （淋病） （AIDS、CA、生殖器疱疹） HPV分型——基因组的分子杂交 已确定基因组全序列：>80种（其中20种证实与宫颈肿瘤相关） 序列未清：>50种 共140多种 侵犯泌尿生殖道上皮的有35个型以上 免疫功能低下及外伤者易感染HPV HPV分型与相关疾病 分型 相关疾病 黏膜类 低危型 6,11,13,32,34,40,42,43,44,53,54… 尖锐湿疣, 肛门生殖器表皮内肿物 高危型 16,18,30,31,33, 35,39… 宫颈癌,肛门生殖器癌,鲍文样丘疹病 皮肤类 低危型 1,2,3,4,7,10,12, 15… 寻常疣,扁平疣,跖疣 高危型 5,8,14,17,20,36, 38… 疣状表皮发育不良 HPV感染（国外） 正常女性中，HPV检出率以1.5%~44.3%不等 男性尿道、肛周部位HPV阳性率12%~28% 在性活跃成人的一生中，50%~75%的人感染过1种以上的HPV病毒，多数是亚临床或潜伏感染 没有症状的成年妇女中，宫颈HPV的检出率高达80% HPV感染（国内） 柯吴坚等对90例临床样本采用PCR技术检测尿道或宫颈拭子HPV DNA，结果在这些就诊者中，HPV DNA阳性13例（14.4%），男性HPV阳性率为8.3%，女性为26.7%，二者差异有统计学意义。 柯吴坚,车雅敏等.性病门诊人乳头瘤病毒感染的流行病学调查[J]. 中国性科学,2009,18(11):12-15 HPV感染的临床过程 HPV感染的发生与转归与机体免疫状态密切相关，绝大多数人群感染HPV是一过性的，暂时性的，即HPV可以被机体自身的免疫系统所清除，所以临床上许多HPV引起的疾病不经治疗也可以自然消退。如寻常疣（刺瘊，中医称千日疮，3年自消）、扁平疣（1~2年消退）、CA（10%~18%自行消退）。 HPV感染临床分型 典型（显性）感染：有临床症状 亚临床感染：临床上肉眼不易辨认的皮损，需要借助放大镜、内窥镜或醋酸白试验才能观察到，组织学和细胞学检查有典型HPV感染的改变，自觉症状缺如。 潜伏（隐性）感染：指HPV进入皮肤黏膜后，不引起任何临床表现，也不引起组织学和细胞学改变的一种HPV存在状态，醋酸白试验阴性，而通过分子生物学方法可在局部皮肤黏膜检测出HPV感染。 距CA皮损更远处存在亚临床和潜伏感染病灶 A B C A：肉眼观察到的CA皮损 B：5%醋酸白试验，阳性部位与肉眼皮损一致 C：ALA-PDD辅助荧光诊断，可见距肉眼皮损中心0.5cm和1cm处，均呈现砖红色荧光，提示存在亚临床和潜伏的HPV感染病灶 * 。 这是ALA-PDD荧光诊断临床研究的图片。ALA-PDD是将ALA溶液敷于皮损及其周围皮肤粘膜2cm，2h后再用波长410nm激光照射，进行荧光诊断 . 左边这张图片是临床肉眼观察到的尖锐湿疣皮损，中间的图片是5%醋酸白试验结果，阳性部位与肉眼皮损一致。。 右边的图片是ALA-PDD的诊断照片，临床肉眼只可看到一个疣体，但经过ALA-PDD诊断后，即C图可以看到一共有5个病灶，在皮损周围0.5cm和1cm（黄箭头所示）处均出现砖红色荧光，提示HPV亚临床和潜伏的感染病灶存在。所以，通过最新的ALA-PDD诊断技术发现，它们的实际发生情况比常用检测方法得到的结果更严重，可存在于距肉眼皮损更远、更广泛的地方。 美国尖锐湿疣发病率（/10万） 欧洲女性尖锐湿疣发病率（/10万） 我国上世纪50年代，尖锐湿疣发病率极低，中国医学科学院皮肤病研究所从1954年到1966年只发现26例尖锐湿疣。 上海第一医学院从1949年至1954年发现86例尖锐湿疣。 我国尖锐湿疣发病情况 自我国改革开放以来，尖锐湿疣的发病率逐年上升，截止到2004年，我国31个省(直辖市、自治区)共累计报告的CA病例数为151 000例，发病率为11.64/10万，占报告STD人数20.35%，排在报告的7种STD的第三位。 重视CA的理由 发病率高 复发率高 与生殖器癌发生密切 显性感染 亚临床感染：外观正常，醋酸白试验（+） 隐性感染： 外观正常，醋酸白试验（-）， 分子生物学检测（+），有传染性，可能亚临床感染显性感染 实验室检查 醋酸白试验：5%醋酸3~5min，肛周15min 可与放大镜或阴道镜结合应用 原理：被HPV感染的上皮细胞角蛋白与醋酸发生凝固反应而变白 应用：辅助不典型皮损的诊断 发现早期极小的损害 检测宫颈亚临床感染 对高危人群进行亚临床感染的筛查 醋酸白试验的假阳性：可高达25% 尿道炎、包皮龟头炎上皮增厚 假阳性：变白区界限不清，不规则 组织病理 特征：空泡细胞（Koilocyte） 其他实验室检测 免疫组化：检测HPV抗原 分子生物学方法：检测HPV DNA PCR 分子杂交 诊断 接触史 临床表现 实验室检查： 醋酸白试验 组织病理 免疫组化 分子生物学方法 鉴别诊断 珍珠样阴茎丘疹 女阴假性湿疣 皮脂腺异位症 鲍文样丘疹病 扁平湿疣 疣状癌 生殖器鳞癌…… 治疗 目的：去除疣体，改善症状和体征 原则： 合并其他STD的检查和治疗 性伴的检查和治疗 治疗期间避免性生活 告知复发情况和随访的重要性 个体化治疗和联合治疗！ 治疗规范（卫生部2008年） 局部药物治疗 0.5%足叶草毒素酊：即 0.5%鬼臼毒素酊 5%咪喹莫特霜 5% 5-氟尿嘧啶霜 三氯醋酸液 物理治疗和手术治疗 液氮冷冻 CO2激光 光动力治疗：外用盐酸氨酮戊酸加半导体或氦氖激光治疗，特别适用于尿道口尖锐湿疣的治疗 手术切除 全身治疗 干扰素：具有广谱抗病毒和免疫调节作用。有干扰素α、β、γ等不同种类，可局部外用、系统给药（肌注或皮下注射）、皮损内注射。因对其疗效尚缺乏确切的评价，且治疗费用较高，一般不推荐常规应用。系统性副作用常见，包括头痛、发热、肌痛等流感样症状，一过性白细胞减少。 白细胞介素-2 聚肌胞 静脉应用抗病毒药、干扰素、胸腺肽、自体疣移植不规范! HPV疫苗 国外已有HPV疫苗：针对HPV16、18、6、11的四价疫苗和HPV16、18的二价疫苗。推荐初次发生性生活前的青春期女性接种，对9岁~26岁的女性有意义，对30岁以上妇女意义不大。疫苗作为宫颈癌的一级预防仍存在争议。 尖锐湿疣抗复发治疗中的误区 盲目抗病毒治疗，追求多疗程治疗 为增强机体免疫力，大剂量多疗程使用免疫增强剂 * 目前某些性病防治机构，动不动就让病人一个疗程又一个疗程的使用广谱抗病毒药物，比如阿昔洛韦等，还有如病毒唑、聚肌胞之类，而这些抗病毒的广谱药物仅对疱疹病毒疗效是比较肯定的，而对尖锐湿疣病毒没有特异性，疗效很差。 在增强机体的免疫力上下了很大的功夫，大剂量多疗程地使用免疫增强剂；实际上尖锐湿疣病毒在临床上引起的感染只局限于局部的皮肤粘膜组织，不至于引起机体的全身免疫力降低。对尖锐湿疣实际上起到作用的是局部细胞免疫，而不是全身免疫，但目前使用的免疫增强剂的药理作用主要是增强全身免疫，所以对治疗尖锐湿疣的作用不是很强。 防治复发策略 去除各种危险因素或相关因素(评估和健康教育） 去除病因 ---人类乳头瘤病毒（治疗） * Many patients either fail to respond to treatment or recurs after adequate response. Recurrence rate of cervical dysplasia in women is not altered by treatment of sexual partners Use condoms during sex. Treatment In the absence of genital warts or cervical SIL, treatment is not recommended for subclinical genital HPV infection, whether it is diagnosed by colposcopy, biopsy, acetic acid application, or through the detection of HPV by laboratory tests. Genital HPV infection frequently goes away on its own, and no therapy has been identified that can eradicate infection. In the presence of coexistent SIL, management should be based on histopathologic findings. 评估 临床评估－确保诊断和治疗正确性 评估内容： * 皮损：大小，数目，位置，与原皮损关系 * 组织病理、HPV分型诊断（必要时） * 鉴别诊断： 鲍温样丘疹病、扁平湿疣等 * 5%冰醋酸试验：有助诊断和确定范围 * ACETIC ACID TEST Following application of 5% acetic acid, HPVlesions may turn greyish white for a few minutes. As the test has poor specificity it is only recommended for use in specialist settings where colposcopy is available, and is not recommended for screening purposes. However, it may be valuable in identifying lesions for targeted biopsy and for demarcating lesions during surgical therapy. False positive results are commonly due to inflammatory conditions (for example, lichen sclerosus et atrophicus, lichen planus, psoriasis, balanoposthitis and vulvovaginitis, eczema, genital herpes, and traumatic microabrasions) and give rise to ragged,irregular acetowhite borders. There may be varying degrees of underlying hyperaemia and capillaries lack the vascular punctuation suggestive of HPV. Differential diagnosis pearly penile papule、molluscum contagiosum, fibroepitheliomata, and seborrhoeic keratoses. 复发相关因素评估 * 影响机体免疫的诸多基础疾病 * 性行为与避孕 * 婚姻、妊娠状况（性伴情况） * 吸烟与饮酒 * 伴患其他性病、包皮过长、外阴阴道感染 （局部潮湿、温热环境） * 皮损大小和病程 * 个人不良卫生习惯、焦虑、教育程度 健康宣教 复发并不可怕，正确认识危害性； 积极消除不利因素，提高机体抵抗力； 了解传染途径和特点； 增强家庭和社会责任感： 避免过早性交，控制性滥行为； 保持健康／卫生的生活方式： 不吸烟／饮酒，劳逸结合，乐观／心情舒畅 * 治疗可能接种的各种女性疾病，如宫颈炎、阴道炎和外阴炎。 治疗包皮过长（包皮、冠状沟内温暖和潮湿的环境也为人类乳头瘤病毒的繁殖提供了良好的条件），对于反复发作的男性患者，要考虑行包皮环切术。 It is controversial whether condom use can prevent HPV transmission. Condoms cover only the penis; HPV may be found elsewhere on the sexual organs (i.e. scrotal sac, anus). The female condom may be more helpful. 健康宣教 早期诊断、及时治疗 皮损小／少，病程短，易治疗 定期复查，坚持治疗、随时自检 随时观察有无新病变， 定期看医生 说服性伴侣检查和治疗，减少再感染机会 大多数患者再感染与性伴HPV感染有关， 对性伴定期检查，与HPV感染者避免性接触 * Further Outpatient Care: Patient should have a follow-up visit with OB/GYN (female) or with urology (male) within 1 week. Treat patient using medications and, if ineffective, with cryotherapy, curettage, electrodesiccation, surgical excision, carbon dioxide laser treatment, or combination therapy. Evaluate and treat sexual partner(s). Perform workup for HPV and other STDs. Search for immunosuppression in patients with treatment failures and recurrences. Look for biopsy recurrences and treatment failures 治疗—key points 治疗由医生和患者共同协商确定 大多治疗方案将在1-6月内清除大多数病人的皮损,但还是 有1/3患者持续感染 家庭治疗可以作为初发疣的一线治疗 皮疹少而小可以用一线治疗 * Acuminate warts respond in up to 90% but papular and macular lesions in only 50% of cases + Few, small lesions can be easily treated under local anaesthesia by scissors excision, diathermy, cryotherapy, or TCA TCA should not be used on large lesions and multiple sessions are not well tolerated by patients + Lesions occurring at new sites during treatment or after clearance,do not necessitate a change of the treatment modality + Persistence or reappearance of the treated lesion is usually an indication to switch to another treatment modality + Patients should be evaluated regularly until the warts are cleared + Patients should be informed that periods of coital rest throughout the course of the therapy might reduce therapy related symptoms such as pain or discomfort. Clinicians who treat patients should be knowledgeable about, and have available, at least one home therapy and one office therapy. Choice of therapy depends on the morphology and extent of warts and should be made by mutual agreement between the physician and the patient. * TCA 不能用于大而多的皮损 * 治疗过程中出现新皮疹不一定要改变治疗方法 * 治疗后皮损持续存在或反复出现时应改变治疗方法 * 告知病人定期评估 * 告知病人在治疗期间暂停性交 * Acuminate warts respond in up to 90% but papular and macular lesions in only 50% of cases + Few, small lesions can be easily treated under local anaesthesia by scissors excision, diathermy, cryotherapy, or TCA TCA should not be used on large lesions and multiple sessions are not well tolerated by patients + Lesions occurring at new sites during treatment or after clearance,do not necessitate a change of the treatment modality + Persistence or reappearance of the treated lesion is usually an indication to switch to another treatment modality + Patients should be evaluated regularly until the warts are cleared + Patients should be informed that periods of coital rest throughout the course of the therapy might reduce therapy related symptoms such as pain or discomfort. Clinicians who treat patients should be knowledgeable about, and have available, at least one home therapy and one office therapy. Choice of therapy depends on the morphology and extent of warts and should be made by mutual agreement between the physician and the patient. 病人告知—key points 患者必须接收清楚的书面信息： 尖锐湿疣的病因、治疗（包括疗程）、预期结 果、可能的并发症（包括复发的可能） 女性患者必须定期作宫颈细胞学检查 由于传染后潜伏期可以较长，6个月内接触的性伴 侣都应监测评估和接受教育 * PATIENT COUNSELLING Information and counselling are fundamental to proper management and need to be non-judgmental, supportive, and focus on the nature of the disease, therapy expectations, and a balanced perspective on sexual issues. + Patients should receive clear information, preferably written, as to the cause, treatment, outcomes, and possible complications of anogenital warts + Reassure patients that although wart clearance may take 1–6 months and recurrences may occur, complete clearance will occur sooner or later + Smokers with recalcitrant lesions should stop smoking as a correlation exists with wart development49 + Advise female patients about regular participation in cervical cytology screening programmes. Reassure that risk of cervical cancer is low and ample time exists for detection and removal of any CIN + Encourage patients to use barrier protection with new sexual contacts until successful treatment has been completed. The use of condoms within a stable relationship may not be needed as the partner will already have been exposed to the infection by the time of consultation. Condom use does not influence the outcome of HPV associated morbidity once infection has become established in the individual + Owing to long latency periods after transmission, the development of condylomas in only one partner in a steady relationship does not inevitably signify sexual contact outside that relationship + Current partners and, if advisable, other partners within the past 6 months, should be assessed for the presence of lesions and for education and counselling about STDs and their prevention 我国新的CA诊疗中： 在治疗原则方面强调 禁止性生活（包括使用避孕套） 使用“安全套”并不安全，目前新的检查和方法证明“安全套”对HPV感染的预防效果是 0%。 * PATIENT COUNSELLING Information and counselling are fundamental to proper management and need to be non-judgmental, supportive, and focus on the nature of the disease, therapy expectations, and a balanced perspective on sexual issues. + Patients should receive clear information, preferably written, as to the cause, treatment, outcomes, and possible complications of anogenital warts + Reassure patients that although wart clearance may take 1–6 months and recurrences may occur, complete clearance will occur sooner or later + Smokers with recalcitrant lesions should stop smoking as a correlation exists with wart development49 + Advise female patients about regular participation in cervical cytology screening programmes. Reassure that risk of cervical cancer is low and ample time exists for detection and removal of any CIN + Encourage patients to use barrier protection with new sexual contacts until successful treatment has been completed. The use of condoms within a stable relationship may not be needed as the partner will already have been exposed to the infection by the time of consultation. Condom use does not influence the outcome of HPV associated morbidity once infection has become established in the individual + Owing to long latency periods after transmission, the development of condylomas in only one partner in a steady relationship does not inevitably signify sexual contact outside that relationship + Current partners and, if advisable, other partners within the past 6 months, should be assessed for the presence of lesions and for education and counselling about STDs and their prevention CA的判愈标准 治疗后的随访很重要！ 尖锐湿疣的潜伏期一般指南中为1-8个月，平均3个月。实际按不同的报告，尖锐湿疣的潜伏期可以是0.5个月至20个月，平均2-4个月。 因此尖锐湿疣的判愈标准确实难定。 联合用药 物理疗法&化学疗法 冷冻 咪喹莫特 或激光 + 或TCA 或电烧 或鬼臼毒素 或光动力 物理疗法&免疫疗法 电烧 +干扰素局部应用 激光 引起CA复发的相关因素 HPV亚临床感染和潜伏感染 机体免疫力低下 性行为 伴发其他STD 包皮过长 病毒载量 性激素水平 使用避孕套 心理因素 治疗不彻底 特殊部位CA 其他 HPV亚临床感染和潜伏感染 Rozmus-Warcholińska等报道，性活跃人群中，至少有80%的人感染过1种或多种类型的HPV，其中接近15％的感染为SPI或LPI，而只有1%出现临床典型的CA表现。Muckerman对249名HPV高危人群的检测发现，宫颈部SPI感染率为10.4%。 HPV亚临床感染和潜伏感染 曹霞等对129例患有宫颈糜烂和外阴湿疣者的检测结果表明：宫颈部SPI感染率分别为22.7％和53.1％。李季等采用PCR技术对375例宫颈糜烂者进行检测发现：LPI感染率为31.2%，明显高于对照组的9.14%。 HPV亚临床感染和潜伏感染 SPI或LPI患者具有传染性，成为潜在的病毒携带者，通过性接触或自身接种而感染他人或自己，并在一定条件下（如机体免疫功能下降）可发展为显性感染，这是CA复发的重要因素之一。但传统的治疗方法（如冷冻、手术等）只能去除肉眼可见的疣体，未能对SPI和LPI部位进行治疗。 机体免疫力低下 机体对HPV的免疫，主要以细胞免疫为主。细胞免疫的有效建立涉及病毒抗原的提呈、免疫细胞的活化、效应细胞清除感染细胞的能力等，主要依靠T淋巴细胞及其亚群、朗格汉斯细胞（Langerhans cell，LC）、自然杀伤细胞、细胞因子等起作用。CA患者体内及局部皮肤黏膜存在不同程度的细胞免疫功能障碍，而复发CA患者的细胞免疫功能下降更是明显。 机体免疫力低下 车雅敏等用流式细胞仪和免疫组化方法对CA患者外周血和皮损分别进行T淋巴细胞亚群的检测，结果发现：CA患者存在全身和局部的细胞免疫功能低下，特别是局部细胞免疫功能低下在CA的复发中起着一定的作用。 车雅敏等. 临床皮肤科杂志,2005,34(1):23 机体免疫力低下 另外，车雅敏等对34例CA患者皮损经CD1α单克隆抗体免疫组化染色后的切片进行LC含量分析，数据表明：不论是初发还是复发CA皮损LC的含量较正常人均明显降低，而且复发CA皮损LC含量也低于初发CA，说明局部LC的减少与CA的发病和复发相关。 车雅敏等. 临床皮肤科杂志,2005,34(1):23 机体免疫力低下 免疫功能低下的人群，如长期应用免疫抑制剂和糖皮质激素者、化疗者及糖尿病、恶性肿瘤、红斑狼疮、艾滋病等患者，CA发病和复发的几率均增加。de la Fuente SG等研究发现与免疫功能正常的人相比，免疫力低下人群（如艾滋病、白血病、接受器官移植者等）CA复发率更高，复发的时间更短。 机体免疫力低下 因此提示在治疗CA时，特别对于CA频繁复发者，不仅要积极寻找可能降低患者全身免疫功能的因素，而且更要重视局部免疫功能的调节，在常规治疗的基础上配合局部应用干扰素和白细胞介素等细胞因子或免疫调节剂如咪喹莫特等，以增强患者局部的细胞免疫反应，提高治疗效果。 性行为 直接性接触是感染HPV的主要途径，同时也是导致CA复发的重要因素之一。研究表明，一生中性伴数越多、性交越频繁、首次性交年龄越小，都会导致CA发病率及复发率增加。Oh等对171位HPV阴性的女学生进行跟踪调查发现，有30.0%的女学生在首次性交后检测出HPV，证明性行为是HPV感染的主要途径。 性行为 Habel等研究发现，在5年内有不少于5个性伴的女性，其CA的发病率是只有1个性伴女性的7.5倍，而复发率是后者的12.8倍。因此，对高危人群进行健康教育，提倡安全性行为，是阻断HPV感染和CA复发的主要途径。 伴发其他STD CA同时伴发其他STD，如淋病、生殖道衣原体感染、梅毒、生殖器疱疹、艾滋病、滴虫病、念珠菌感染等，可降低CA患者体内及局部的抗病能力，增加CA的复发率。特别是梅毒、生殖器疱疹等糜烂溃疡性STD，引起局部黏膜屏障受到损害，更利于HPV的侵入、繁殖与生长，从而使CA发病和复发的几率成倍增加。 伴发其他STD Höpfl等报道：HIV阳性的男性与HIV阴性的男性相比，高危型HPV（HPV -16、-18、-31）的感染率更高，而25.4%并发CA的HIV阴性男性，检测出的HPV类型绝大多数为低危型HPV（HPV-6、-11）。 性激素水平 CA的复发可能受到体内性激素水平的影响。妇女在妊娠期间不仅更易感染HPV，而且CA体积也会明显增大，形成巨大型CA（Buschke-Löwenstein tumor），增加治疗难度。 性激素水平 这可能是因为人体在怀孕期间，体内激素水平改变，细胞免疫功能受到生理性抑制，从而使体内环境更有利于胎儿存活。但这种生理性的免疫抑制状态，会干扰机体的抗病毒能力，此外，妊娠期间疣体血供增加，阴道分泌物增多，局部潮湿，均有利于HPV繁殖，引起巨大型CA，且治疗后容易复发。 病毒载量 在临床中发现，并不是所有接触CA患者的人都会被感染HPV，这可能与接触的病毒载量、病期以及个体的免疫状态等多种因素有关，其中病毒载量与CA复发可能存在一定的相关性。 病毒载量 Che等采用实时荧光定量PCR技术对63例CA患者进行检测，结果显示：复发CA组平均HPV6/11 DNA载量高于初发CA组，差异具有显著性，HPV6/11 DNA的载量随着复发次数以及病程的增加而升高，呈正相关，说明病毒载量在CA复发中起着一定的作用。 Ya-Min Che,et al . International Journal of STD & AIDS, 2005,16:605-7 病毒载量 因此在CA的治疗中，对于高病毒载量的患者应强调采取早期综合抗病毒治疗，使病毒载量尽可能下降，从而达到减少复发的目的。 包皮过长 包皮过长可引起龟头和冠状沟部位温度、湿度增加及包皮垢形成增多，为病原微生物的生长创造良好条件，并增加HPV感染的几率。多项研究表明，进行包皮环切术可减少阴茎部位HPV感染以及与HPV感染相关的阴茎癌的风险性，并且其性伴患宫颈癌的风险性比包皮过长者的性伴更小。 心理因素 CA反复发作，常常给患者及其家人带来了严重的心理问。医务人员在防治CA的时候往往忽视患者心理感受。绝大多数CA患者常表现出强烈的恐惧和负罪感，而再次复发患者常产生抑郁、焦虑等心理障碍，甚至出现厌世情绪。患者的不良情绪可以影响机体的免疫功能，引起细胞免疫功能低下，使病毒复制增加，再加上不适当地过度清洁，破坏局部的皮肤黏膜屏障，导致CA容易复发。 心理因素 因此，临床上对于CA患者，除了一般常规的治疗手段外，应配合进行心理和精神上的干预治疗，解除患者不必要的精神负担，使患者树立起战胜疾病的信心，正确对待该病，对减少和防止CA复发具有重要意义。 CA治疗不彻底 CA治疗不彻底，可由于医生的治疗水平或责任心不足、患者处于亚临床感染或隐性感染等因素引起。因此在进行物理治疗时，治疗范围最好超过疣体基底周围2cm左右，或用醋酸白试验显示亚临床感染灶，或在物理治疗的基础上局部配合免疫调节剂等，以便能进行更好的彻底治疗。 特殊部位的CA 特殊部位的CA（如尿道口和宫颈口），一般的治疗方法效果欠佳、难度大、并发症多，使该部位成为HPV潜伏灶，是HPV传播及CA复发的一个不容忽视的因素，因此在治疗这些特殊部位时可请相关科室（如泌尿科和妇产科等）协助也可应用ALA-PDT治疗。 ALA-PDT（氨基酮戊酸-光动力） ALA是体内HB合成过程中的前体，正常时含量小，无光敏性 外源性ALA进入人体，选择性地被增生活跃的细胞（HPV感染细胞）吸收，在细胞内转化为原卟啉Ⅸ 原卟啉Ⅸ是一种很强的光敏剂，经红光照射后产生活性氧杀死增生活跃的细胞，而对周围正常组织损伤轻微。 其他 口服避孕药是否会增加HPV的感染和CA的复发存在着争议。Schmeink等研究表明长期口服避孕药者会增加HPV的转录、减少HPV的清除、有利于HPV的长期存在。Lenselink等研究显示女性口服激素类避孕药并不会增加HPV的感染风险。 其他 酗酒能降低人体的免疫力，是导致尖锐湿疣复发的危险因素之一。饮酒者常在酒精的作用下，社交行为增加，性欲增强，性伴数增多，性暴力增多，生殖器损伤的机会和程度增加，因此增加了CA发病和复发。 其他 吸烟同样可降低机体的免疫力，从而增加CA发病和复发的机率。Nielson等研究表明，每天大量吸烟（≧10根）可增加HPV的感染风险性。Lenselink等报道，不吸烟女性HPV检测的阳性率为17.8%，吸烟者为28.3%。 小结 CA的复发并不可怕，只要正确认识该病的特点，做好预防工作，就可有效的减少CA复发。建议做到如下几方面： 1、避免再接触感染源，同时对高发年龄段及高危人群加强性知识教育，提高自我防护意识、避免过早性交、减少性伴数、洁身自爱； 2、早发现、早治疗，治疗中注意HPV亚临床感染或隐性感染、合并STD及伴发其他系统疾病等问题，医生应根据患者具体情况选择合适的治疗方法，采用联合治疗方案，必要时可请相关科室协助； 小结 3、医生应对CA患者进行性病方面仔细、全面的检查，对合并的其他性病要同时给予规范治疗； 4、患者在治疗期间应避免性生活； 5、夫妻或性伴同时进行彻底治疗； 6、保持健康的生活方式，不吸烟、不饮酒，增强机体抵抗力，解除思想顾虑，保持身心健康，树立起战胜疾病的信心； 小结 7、治疗后要定期复查，特别是治疗后3个月内； 8、对包皮过长及包茎者在治愈后应做包皮环切术； 9、预防间接感染，提倡不用公用毛巾、浴巾，不在公用浴缸中沐浴，注意个人局部卫生，保持局部干燥和清洁，对分泌物污染的衣物要进行消毒处理。 小结 总之，医务人员在治疗CA的过程中，应考虑到各种可能促使CA复发的因素，从而采取相应的措施，以便有效地减少CA的复发。 * 。 这是ALA-PDD荧光诊断临床研究的图片。ALA-PDD是将ALA溶液敷于皮损及其周围皮肤粘膜2cm，2h后再用波长410nm激光照射，进行荧光诊断 . 左边这张图片是临床肉眼观察到的尖锐湿疣皮损，中间的图片是5%醋酸白试验结果，阳性部位与肉眼皮损一致。。 右边的图片是ALA-PDD的诊断照片，临床肉眼只可看到一个疣体，但经过ALA-PDD诊断后，即C图可以看到一共有5个病灶，在皮损周围0.5cm和1cm（黄箭头所示）处均出现砖红色荧光，提示HPV亚临床和潜伏的感染病灶存在。所以，通过最新的ALA-PDD诊断技术发现，它们的实际发生情况比常用检测方法得到的结果更严重，可存在于距肉眼皮损更远、更广泛的地方。 * 目前某些性病防治机构，动不动就让病人一个疗程又一个疗程的使用广谱抗病毒药物，比如阿昔洛韦等，还有如病毒唑、聚肌胞之类，而这些抗病毒的广谱药物仅对疱疹病毒疗效是比较肯定的，而对尖锐湿疣病毒没有特异性，疗效很差。 在增强机体的免疫力上下了很大的功夫，大剂量多疗程地使用免疫增强剂；实际上尖锐湿疣病毒在临床上引起的感染只局限于局部的皮肤粘膜组织，不至于引起机体的全身免疫力降低。对尖锐湿疣实际上起到作用的是局部细胞免疫，而不是全身免疫，但目前使用的免疫增强剂的药理作用主要是增强全身免疫，所以对治疗尖锐湿疣的作用不是很强。 * Many patients either fail to respond to treatment or recurs after adequate response. Recurrence rate of cervical dysplasia in women is not altered by treatment of sexual partners Use condoms during sex. Treatment In the absence of genital warts or cervical SIL, treatment is not recommended for subclinical genital HPV infection, whether it is diagnosed by colposcopy, biopsy, acetic acid application, or through the detection of HPV by laboratory tests. Genital HPV infection frequently goes away on its own, and no therapy has been identified that can eradicate infection. In the presence of coexistent SIL, management should be based on histopathologic findings. * ACETIC ACID TEST Following application of 5% acetic acid, HPVlesions may turn greyish white for a few minutes. As the test has poor specificity it is only recommended for use in specialist settings where colposcopy is available, and is not recommended for screening purposes. However, it may be valuable in identifying lesions for targeted biopsy and for demarcating lesions during surgical therapy. False positive results are commonly due to inflammatory conditions (for example, lichen sclerosus et atrophicus, lichen planus, psoriasis, balanoposthitis and vulvovaginitis, eczema, genital herpes, and traumatic microabrasions) and give rise to ragged,irregular acetowhite borders. There may be varying degrees of underlying hyperaemia and capillaries lack the vascular punctuation suggestive of HPV. Differential diagnosis pearly penile papule、molluscum contagiosum, fibroepitheliomata, and seborrhoeic keratoses. * 治疗可能接种的各种女性疾病，如宫颈炎、阴道炎和外阴炎。 治疗包皮过长（包皮、冠状沟内温暖和潮湿的环境也为人类乳头瘤病毒的繁殖提供了良好的条件），对于反复发作的男性患者，要考虑行包皮环切术。 It is controversial whether condom use can prevent HPV transmission. Condoms cover only the penis; HPV may be found elsewhere on the sexual organs (i.e. scrotal sac, anus). The female condom may be more helpful. * Further Outpatient Care: Patient should have a follow-up visit with OB/GYN (female) or with urology (male) within 1 week. Treat patient using medications and, if ineffective, with cryotherapy, curettage, electrodesiccation, surgical excision, carbon dioxide laser treatment, or combination therapy. Evaluate and treat sexual partner(s). Perform workup for HPV and other STDs. Search for immunosuppression in patients with treatment failures and recurrences. Look for biopsy recurrences and treatment failures * Acuminate warts respond in up to 90% but papular and macular lesions in only 50% of cases + Few, small lesions can be easily treated under local anaesthesia by scissors excision, diathermy, cryotherapy, or TCA TCA should not be used on large lesions and multiple sessions are not well tolerated by patients + Lesions occurring at new sites during treatment or after clearance,do not necessitate a change of the treatment modality + Persistence or reappearance of the treated lesion is usually an indication to switch to another treatment modality + Patients should be evaluated regularly until the warts are cleared + Patients should be informed that periods of coital rest throughout the course of the therapy might reduce therapy related symptoms such as pain or discomfort. Clinicians who treat patients should be knowledgeable about, and have available, at least one home therapy and one office therapy. Choice of therapy depends on the morphology and extent of warts and should be made by mutual agreement between the physician and the patient. * Acuminate warts respond in up to 90% but papular and macular lesions in only 50% of cases + Few, small lesions can be easily treated under local anaesthesia by scissors excision, diathermy, cryotherapy, or TCA TCA should not be used on large lesions and multiple sessions are not well tolerated by patients + Lesions occurring at new sites during treatment or after clearance,do not necessitate a change of the treatment modality + Persistence or reappearance of the treated lesion is usually an indication to switch to another treatment modality + Patients should be evaluated regularly until the warts are cleared + Patients should be informed that periods of coital rest throughout the course of the therapy might reduce therapy related symptoms such as pain or discomfort. Clinicians who treat patients should be knowledgeable about, and have available, at least one home therapy and one office therapy. Choice of therapy depends on the morphology and extent of warts and should be made by mutual agreement between the physician and the patient. * PATIENT COUNSELLING Information and counselling are fundamental to proper management and need to be non-judgmental, supportive, and focus on the nature of the disease, therapy expectations, and a balanced perspective on sexual issues. + Patients should receive clear information, preferably written, as to the cause, treatment, outcomes, and possible complications of anogenital warts + Reassure patients that although wart clearance may take 1–6 months and recurrences may occur, complete clearance will occur sooner or later + Smokers with recalcitrant lesions should stop smoking as a correlation exists with wart development49 + Advise female patients about regular participation in cervical cytology screening programmes. Reassure that risk of cervical cancer is low and ample time exists for detection and removal of any CIN + Encourage patients to use barrier protection with new sexual contacts until successful treatment has been completed. The use of condoms within a stable relationship may not be needed as the partner will already have been exposed to the infection by the time of consultation. Condom use does not influence the outcome of HPV associated morbidity once infection has become established in the individual + Owing to long latency periods after transmission, the development of condylomas in only one partner in a steady relationship does not inevitably signify sexual contact outside that relationship + Current partners and, if advisable, other partners within the past 6 months, should be assessed for the presence of lesions and for education and counselling about STDs and their prevention * PATIENT COUNSELLING Information and counselling are fundamental to proper management and need to be non-judgmental, supportive, and focus on the nature of the disease, therapy expectations, and a balanced perspective on sexual issues. + Patients should receive clear information, preferably written, as to the cause, treatment, outcomes, and possible complications of anogenital warts + Reassure patients that although wart clearance may take 1–6 months and recurrences may occur, complete clearance will occur sooner or later + Smokers with recalcitrant lesions should stop smoking as a correlation exists with wart development49 + Advise female patients about regular participation in cervical cytology screening programmes. Reassure that risk of cervical cancer is low and ample time exists for detection and removal of any CIN + Encourage patients to use barrier protection with new sexual contacts until successful treatment has been completed. The use of condoms within a stable relationship may not be needed as the partner will already have been exposed to the infection by the time of consultation. Condom use does not influence the outcome of HPV associated morbidity once infection has become established in the individual + Owing to long latency periods after transmission, the development of condylomas in only one partner in a steady relationship does not inevitably signify sexual contact outside that relationship + Current partners and, if advisable, other partners within the past 6 months, should be assessed for the presence of lesions and for education and counselling about STDs and their prevention