生殖器疣是良性疾病而且有自发消退的可能,因此并非都需要治疗。[3]Wiley DJ, Douglas J, Beutner K, et al. External genital warts: diagnosis, treatment, and prevention. Clin Infect Dis. 2002 Oct 15;35(Suppl 2):S210-24.https://academic.oup.com/cid/article/35/Supplement_2/S210/316436http://www.ncbi.nlm.nih.gov/pubmed/12353208?tool=bestpractice.com[30]Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137. [Erratum in: MMWR Recomm Rep. 2015 Aug 28;64(33):924.]https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com 一旦患者和医生确定需要治疗,治疗方法根据患者和医生的倾向性确定。
在决定治疗方法方面起作用的因素包括:疣的位置、受累部位的表面范围、疣的形态、对先前治疗的反应、希望自我给药还是医生给药、治疗成本、不良反应、共存疾病和医生经验。[7]Brown TJ, Yen-Moore A, Tyring SK. An overview of sexually transmitted diseases. Part II. Am Acad Dermatol. 1999 Nov;41(5 Pt 1):661-77.http://www.ncbi.nlm.nih.gov/pubmed/10534627?tool=bestpractice.com[30]Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137. [Erratum in: MMWR Recomm Rep. 2015 Aug 28;64(33):924.]https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com 通常需一个疗程的治疗,而非单次治疗。[6]Beutner KR, Reitano MV, Richwald GA, et al. External genital warts: report of the American Medical Association consensus conference. Clin Infect Dis. 1998 Oct;27(4):796-806.http://www.ncbi.nlm.nih.gov/pubmed/9798036?tool=bestpractice.com[30]Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137. [Erratum in: MMWR Recomm Rep. 2015 Aug 28;64(33):924.]https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com
一般情况下,治疗目标是破坏或移除可见病变。虽然治疗可减少人乳头瘤病毒 (human papillomavirus, HPV) 的传染性,但不能将其根除。[6]Beutner KR, Reitano MV, Richwald GA, et al. External genital warts: report of the American Medical Association consensus conference. Clin Infect Dis. 1998 Oct;27(4):796-806.http://www.ncbi.nlm.nih.gov/pubmed/9798036?tool=bestpractice.com[30]Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137. [Erratum in: MMWR Recomm Rep. 2015 Aug 28;64(33):924.]https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com 没有证据表明,治疗可降低 HPV 的性传播速度。[3]Wiley DJ, Douglas J, Beutner K, et al. External genital warts: diagnosis, treatment, and prevention. Clin Infect Dis. 2002 Oct 15;35(Suppl 2):S210-24.https://academic.oup.com/cid/article/35/Supplement_2/S210/316436http://www.ncbi.nlm.nih.gov/pubmed/12353208?tool=bestpractice.com[30]Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137. [Erratum in: MMWR Recomm Rep. 2015 Aug 28;64(33):924.]https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com
免疫功能正常的患者
目前市面上存在着各种治疗方法,但没有确定明确的一线治疗。没有理想的单一药剂可供所有患者或所有疣病使用。治疗必须以上述众多因素为指导。如果患者在 3 次医生给药治疗后无明显改善,或在 6 次治疗后没有完全清除病变,应使用替代疗法。[6]Beutner KR, Reitano MV, Richwald GA, et al. External genital warts: report of the American Medical Association consensus conference. Clin Infect Dis. 1998 Oct;27(4):796-806.http://www.ncbi.nlm.nih.gov/pubmed/9798036?tool=bestpractice.com[7]Brown TJ, Yen-Moore A, Tyring SK. An overview of sexually transmitted diseases. Part II. Am Acad Dermatol. 1999 Nov;41(5 Pt 1):661-77.http://www.ncbi.nlm.nih.gov/pubmed/10534627?tool=bestpractice.com
鬼臼毒素和咪喹莫特乳膏等外用药剂已作为生殖器疣患者给药的治疗方法,其疗效各有差异。 [
]How does imiquimod compare with placebo in non-immunocompromised adults with anogenital warts?https://cochranelibrary.com/cca/doi/10.1002/cca.970/full显示答案 这些药剂可供患者在家中使用。根据特定药剂,使用的频率和持续时间不同。应密切关注患者是否遵守自行给药治疗,且应视为对特定治疗疗效不佳的可能原因。
患者自我给药疗法
鬼臼毒素的作用原理是通过结合微管的亚基,阻止处于有丝分裂中的细胞分裂。[7]Brown TJ, Yen-Moore A, Tyring SK. An overview of sexually transmitted diseases. Part II. Am Acad Dermatol. 1999 Nov;41(5 Pt 1):661-77.http://www.ncbi.nlm.nih.gov/pubmed/10534627?tool=bestpractice.com 患者可能发现很难将鬼臼毒素外用溶液只施用于生殖器疣部位。对患者而言,鬼臼毒素凝胶更容易涂抹,并已证明具有与外用溶液相同的药效和复发率。[43]Tyring SK, Edwards L, Friedman DJ, et al. Safety and efficacy of 0.5% podofilox gel in the treatment of anogenital warts. Arch Dermatol. 1998 Jan;134(1):33-8.https://jamanetwork.com/journals/jamadermatology/fullarticle/188580http://www.ncbi.nlm.nih.gov/pubmed/9449907?tool=bestpractice.com 局部炎症、灼痛、瘙痒和疼痛为常见不良反应。[3]Wiley DJ, Douglas J, Beutner K, et al. External genital warts: diagnosis, treatment, and prevention. Clin Infect Dis. 2002 Oct 15;35(Suppl 2):S210-24.https://academic.oup.com/cid/article/35/Supplement_2/S210/316436http://www.ncbi.nlm.nih.gov/pubmed/12353208?tool=bestpractice.com
咪喹莫特是一种局部免疫调节剂,可诱导生成细胞因子干扰素α、白介素6 (IL-6)、IL-8 和 α 肿瘤坏死因子 (TNF-α),并导致 T 细胞介导的细胞毒性免疫反应。[7]Brown TJ, Yen-Moore A, Tyring SK. An overview of sexually transmitted diseases. Part II. Am Acad Dermatol. 1999 Nov;41(5 Pt 1):661-77.http://www.ncbi.nlm.nih.gov/pubmed/10534627?tool=bestpractice.com 研究显示,对比安慰剂,咪喹莫特治疗可显著清除疣。与其他治疗(例如鬼臼毒素)相比,其复发率相对较低。[11]Severson J, Evans TY, Lee P, et al. Human papillomavirus infections: epidemiology, pathogenesis, and therapy. J Cutan Med Surg. 2001 Jan-Feb;5(1):43-60.http://www.ncbi.nlm.nih.gov/pubmed/11281434?tool=bestpractice.com 不良反应包括,局部瘙痒、红斑、糜烂、灼痛和疼痛。[4]Czelusta AJ, Evans T, Arany I, et al. A guide to immunotherapy of genital warts: focus on interferon and imiquimod. BioDrugs. 1999 May;11(5):319-32.http://www.ncbi.nlm.nih.gov/pubmed/18031142?tool=bestpractice.com 无瘢痕愈合被认为是此治疗的一大优势。然而,咪喹莫特的使用有时受到成本的限制。每周 3 次在外部肛门生殖器疣涂抹 5% 咪喹莫特软膏的方案是最佳治疗方案。[44]Gotovtseva EP, Kapadia AS, Smolensky MH, et al. Optimal frequency of imiquimod (aldara) 5% cream for the treatment of external genital warts in immunocompetent adults: a meta-analysis. Sex Transm Dis. 2008 Apr;35(4):346-51.http://www.ncbi.nlm.nih.gov/pubmed/18360317?tool=bestpractice.com
赛儿茶素 (Sinecatechins) 软膏,也称为 Polyphenon E,是一种标准化的绿茶提取物,具有免疫刺激、抗增殖和抗肿瘤性质。确切的作用机制还不完全清楚。[45]Tatti S, Stockfleth E, Beutner KR, et al. Polyphenon E: a new treatment for external anogenital warts. Br J Dermatol. 2010 Jan;162(1):176-84.http://www.ncbi.nlm.nih.gov/pubmed/19709100?tool=bestpractice.com[46]Gross G, Meyer KG, Pres H, et al. A randomized, double-blind, four-arm parallel-group, placebo-controlled Phase II/III study to investigate the clinical efficacy of two galenic formulations of Polyphenon E in the treatment of external genital warts. J Eur Acad Dermatol Venereol. 2007 Nov;21(10):1404-12.http://www.ncbi.nlm.nih.gov/pubmed/17958849?tool=bestpractice.com[47]Stockfleth E, Beti H, Orasan R, et al. Topical Polyphenon E in the treatment of external genital and perianal warts: a randomized controlled trial. Br J Dermatol. 2008 Jun;158(6):1329-38.http://www.ncbi.nlm.nih.gov/pubmed/18363746?tool=bestpractice.com 研究显示,完全清除率高达 57.2%。常见不良反应包括,局部红斑、瘙痒、刺激和疼痛。[48]Tatti S, Swinehart JM, Thielert C, et al. Sinecatechins, a defined green tea extract, in the treatment of external anogenital warts; a randomized controlled trial. Obstet Gynecol. 2008 Jun;111(6):1371-9.http://www.ncbi.nlm.nih.gov/pubmed/18515521?tool=bestpractice.com
医生给药的疗法
冷冻疗法通过温度诱导的细胞溶解对疣体形成破坏。研究表明此疗法具有疗效,并且几乎没有不良反应。[49]Bertolotti A, Dupin N, Bouscarat F, et al. Cryotherapy to treat anogenital warts in nonimmunocompromised adults: systematic review and meta-analysis. J Am Acad Dermatol. 2017 Sep;77(3):518-26.http://www.ncbi.nlm.nih.gov/pubmed/28651824?tool=bestpractice.com 冷冻疗法非常疼痛,且一般需要多种治疗配合。
三氯乙酸 (TCA) 是一种可通过化学混凝破坏疣的腐蚀剂。可用于治疗小的生殖器湿疣。复发率高。[50]Godley MJ, Bradbeer CS, Gellen M, et al. Cryotherapy compared with trichloroacetic acid in treating genital warts. Genitourin Med. 1987 Dec;63(6):390-2.http://www.ncbi.nlm.nih.gov/pubmed/3323028?tool=bestpractice.com 此药剂具有明显的细胞破坏能力,必须由医生施用,以防止接触正常皮肤和黏膜。[11]Severson J, Evans TY, Lee P, et al. Human papillomavirus infections: epidemiology, pathogenesis, and therapy. J Cutan Med Surg. 2001 Jan-Feb;5(1):43-60.http://www.ncbi.nlm.nih.gov/pubmed/11281434?tool=bestpractice.com
手术切除可使患者一次就诊就能清除疣体。其可用于局限性、均匀或广泛性疣形成的患者。[6]Beutner KR, Reitano MV, Richwald GA, et al. External genital warts: report of the American Medical Association consensus conference. Clin Infect Dis. 1998 Oct;27(4):796-806.http://www.ncbi.nlm.nih.gov/pubmed/9798036?tool=bestpractice.com 对于多数病例,手术切除可大范围消减受累部位的疣体,因此其可作为多种治疗中的先导治疗。[6]Beutner KR, Reitano MV, Richwald GA, et al. External genital warts: report of the American Medical Association consensus conference. Clin Infect Dis. 1998 Oct;27(4):796-806.http://www.ncbi.nlm.nih.gov/pubmed/9798036?tool=bestpractice.com 方法包括切线式剪刀切除、削除、刮除和电外科手术。
替代疗法包括 CO₂ 激光消融和电灼治疗。同样使得患者一次就诊就能消除疣体。这些更具侵入性的技术对疣累及大面积部位的患者有益。
光动力疗法 (PDT) 联合外用或病变部位用的氨基酮戊酸(一种光敏剂)是一种特定的光化学疗法,已证明可有效治疗外生殖器疣。[51]Ying Z, Li X, Dang H. 5-aminolevulinic acid-based photodynamic therapy for the treatment of condylomata acuminata in Chinese patients: a meta-analysis. Photodermatol Photoimmunol Photomed. 2013 Jun;29(3):149-59.http://www.ncbi.nlm.nih.gov/pubmed/23651275?tool=bestpractice.com 一旦使用,氨基酮戊酸可被快速增殖的 HPV 感染细胞吸收。通过光照激活氨基酮戊酸,同时在有氧条件下形成单态氧,可引起生殖器疣的氧化性损伤和破坏。这是 PDT 一种适应症外的用法。
免疫功能受损的患者
免疫受损患者的生殖器疣可对标准治疗产生耐药,且更可能复发。这一群体的治疗很重要,因为不太可能会自发消退,且转化为鳞状细胞癌的风险增加。[18]Nebesio CL, Mirowski GW, Chuang TY. Human papillomavirus: clinical significance and malignant potential. Int J Dermatol. 2001 Jun;40(6):373-9.http://www.ncbi.nlm.nih.gov/pubmed/11589741?tool=bestpractice.com[52]Czelusta A, Yen-Moore A, Van der Straten M, et al. An overview of sexually transmitted diseases. Part III. Sexually transmitted diseases in HIV-infected patients. J Am Acad Dermatol. 2000 Sep;43(3):409-32.http://www.ncbi.nlm.nih.gov/pubmed/10954653?tool=bestpractice.com 虽然没有特定的指南,但是可能需要进行更长时间的治疗或采用联合治疗。在不同时期对皮损进行临床评估可确定疗程和治疗的侵袭性。手术切除后进行非侵入性治疗可能有必要。可能需要采用其他联合治疗。[53]Orlando G, Fasolo MM, Beretta R, et al. Combined surgery and cidofovir is an effective treatment for genital warts in HIV-infected patients. AIDS. 2002 Feb 15;16(3):447-50.http://www.ncbi.nlm.nih.gov/pubmed/11834957?tool=bestpractice.comHIV 感染患者的疣清除:有中等质量证据表明,电灼法手术切除外加在切除 1 个月内于患处涂抹 1% 西多福韦软膏(每周 5 天,连用 2 周)是治疗 HIV 感染患者生殖器疣的有效方法。100% 接受联合治疗的患者可见疣体完全消退,而在单独接受手术以及单独接受西多福韦的受试者中,此比例分别为 93% 和 76%。[53]Orlando G, Fasolo MM, Beretta R, et al. Combined surgery and cidofovir is an effective treatment for genital warts in HIV-infected patients. AIDS. 2002 Feb 15;16(3):447-50.http://www.ncbi.nlm.nih.gov/pubmed/11834957?tool=bestpractice.com受试者<200名的随机对照临床试验(RCT)、受试者>200名且方法学存在缺陷的随机对照临床试验(RCT)、方法学存在缺陷的系统评价或者高质量的观察性(队列)研究。 据报道,随着抗逆转录病毒药物的使用,潜在 HIV 感染得到改善后,HIV 感染群体中的尖锐湿疣复发率有所降低。[54]Orlando G, Fasolo MM, Signori R, et al. Impact of highly active antiretroviral therapy on clinical evolution of genital warts in HIV-1 infected patients. AIDS. 1999 Feb 4;13(2):291-3.http://www.ncbi.nlm.nih.gov/pubmed/10202844?tool=bestpractice.com
一项随机、双盲、安慰剂对照临床研究表明,局部涂抹 5% 咪喹莫特乳膏可缩小疣体面积,且可能在治疗 HIV 感染个体的外阴疣方面具有临床疗效。但是,使用咪喹莫特的患者的清除率与安慰剂组的清除率无显著差异。[55]Gilson RJ, Shupack JL, Friedman-Kien AE, et al. A randomized, controlled, safety study using imiquimod for the topical treatment of anogenital warts in HIV-infected patients. Imiquimod Study Group. AIDS. 1999 Dec 3;13(17):2397-404.http://www.ncbi.nlm.nih.gov/pubmed/10597781?tool=bestpractice.com 需要进一步研究,才能确定最适合这一患者群体的治疗方法。
体表疣的推荐治疗方案
患者自我给药疗法[30]Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137. [Erratum in: MMWR Recomm Rep. 2015 Aug 28;64(33):924.]https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com
0.5% 鬼臼毒素溶液或凝胶。鬼臼毒素的前一代产品是鬼臼,因含诱变剂,已不再作为常规使用药物。[56]Petersen CS, Weismann K. Quercetin and kaempherol: an argument against the use of podophyllin? Genitourin Med. 1995 Apr;71(2):92-3.http://www.ncbi.nlm.nih.gov/pubmed/7744421?tool=bestpractice.com
5% 咪喹莫特软膏。[44]Gotovtseva EP, Kapadia AS, Smolensky MH, et al. Optimal frequency of imiquimod (aldara) 5% cream for the treatment of external genital warts in immunocompetent adults: a meta-analysis. Sex Transm Dis. 2008 Apr;35(4):346-51.http://www.ncbi.nlm.nih.gov/pubmed/18360317?tool=bestpractice.com
15% 绿茶儿茶素(Polyphenon E;通用名:茶多酚)软膏。[45]Tatti S, Stockfleth E, Beutner KR, et al. Polyphenon E: a new treatment for external anogenital warts. Br J Dermatol. 2010 Jan;162(1):176-84.http://www.ncbi.nlm.nih.gov/pubmed/19709100?tool=bestpractice.com
医生给药治疗[30]Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137. [Erratum in: MMWR Recomm Rep. 2015 Aug 28;64(33):924.]https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com
腔内疣的推荐治疗方案
下列治疗方案建议用于阴道、尿道和肛门疣。[30]Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137. [Erratum in: MMWR Recomm Rep. 2015 Aug 28;64(33):924.]https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com
阴道疣:
尿道疣:[30]Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137. [Erratum in: MMWR Recomm Rep. 2015 Aug 28;64(33):924.]https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com
肛门疣:[30]Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137. [Erratum in: MMWR Recomm Rep. 2015 Aug 28;64(33):924.]https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com
冷冻疗法
0.5% 鬼臼毒素溶液或凝胶
80%-90% TCA
手术切除
CO₂ 激光消融。
妊娠患者
在妊娠期,生殖器疣可能会增生,并且变得容易被刺激。因此,妊娠期可能需要进行预防性切除。生殖器疣可使用破坏性方法进行清除,包括冷冻治疗、手术或激光。[6]Beutner KR, Reitano MV, Richwald GA, et al. External genital warts: report of the American Medical Association consensus conference. Clin Infect Dis. 1998 Oct;27(4):796-806.http://www.ncbi.nlm.nih.gov/pubmed/9798036?tool=bestpractice.com 也可使用 TCA,但 TCA 对湿疣最有效。[6]Beutner KR, Reitano MV, Richwald GA, et al. External genital warts: report of the American Medical Association consensus conference. Clin Infect Dis. 1998 Oct;27(4):796-806.http://www.ncbi.nlm.nih.gov/pubmed/9798036?tool=bestpractice.com
必须避免使用鬼臼毒素,因为其可致畸。咪喹莫特和茶多酚尚未在患生殖器疣的妊娠患者中进行充分研究,因此应避免使用。
HPV 6 和 11 型已被证实与婴儿的喉乳头状瘤有关。但是,生殖器疣并不是进行剖宫产的指征。[57]Chuang TY, Ilstrup DM, Perry HO, et al. Condyloma acuminatum in Rochester, Minnesota, 1950-1978. II. Anaplasias and unfavorable outcomes. Arch Dermatol. 1984 Apr;120(4):476-83.http://www.ncbi.nlm.nih.gov/pubmed/6546657?tool=bestpractice.com 剖宫产仅在罕见的梗阻或出血的情况下进行。