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Genital warts

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Anogenital warts (AGWs) are a very common disease. They are caused mostly by low-risk human papillomaviruses (HPV) 6 and 11, particularly the former. Clinical presentation is mostly of growths in the areas of friction of the anogenital region. The treatment is classified as patient/home applied or administered by a professional. In cases with atypical presentations or resistance to recommended therapies, great care should be taken to establish a differential diagnosis taking into account normal anatomical variations, infectious etiologies, precancers and cancers, as well as benign dermatological growths. The prevention of AGWs can be achieved by the use of the quadrivalent prophylactic HPV vaccine administered prior to sexual debut, as well as the meticulous use of condoms. Where coverage of the quadrivalent vaccine has been high, marked reductions in AGWs are being seen in young women of vaccine-eligible age, as well as in young males (as herd immunity effect).

Introduction

Anogenital warts (AGWs) are caused by human papillomavirus (HPV), particularly genotypes 6 and 11. Condylomata acuminata and condyloma are synonymous terms. They are clinically evident skin or mucosal growths in the anogenital area. They are an important reason for consultation in primary care, dermatology, gynecology, and urology care settings and an important burden on the health-care system because patients often need to visit health-care providers repeatedly for management, as well as major sources of negative psychosexual reactions. The advent of the quadrivalent vaccine, effective against HPV-6/11/16/18, has the potential to drastically change the epidemiology of this condition.

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Epidemiology

Many reports, prior to the introduction of the quadrivalent vaccine as a public health program against HPV infection and disease, showed that AGWs were a common worldwide public health problem affecting young men and young women, although more commonly noted in males. The incidence of AGWs in an HPV vaccine trial's placebo group, which included women from 16 countries, was 0.87 cases per 100 person-years-at-risk (PY) [1]. In a further study of physician and hospital billing as well as the

Etiology

AGWs are mostly caused by HPV. HPVs constitute a large family of >200 genotypes, of which >100 have been sequenced to date. It cannot be cultivated in the traditional way, so diagnosis has relied on molecular techniques. A new HPV is recognized if the complete genome has been cloned and the DNA sequence of the L1 open reading frame differs by >10% from the closest known type. Differences between 2% and 10% homology define a subtype and <2% a variant. Some genotypes have a tropism for skin and

Natural history

The virus is readily transmitted through penetrative and non-penetrative sexual activity (vaginal, anal, and oral; same and opposite sex), and it can also be transmitted through nonsexual genital skin-to-genital skin contact and, occasionally, vertically from mother to child during delivery. On the other hand, in AGWs HPV-6 predominates; of note in recurrent respiratory papillomatosis (RRP), HPV-11 is chiefly responsible [11].

In a cohort of females in the placebo arms of the quadrivalent

Clinical manifestation

AGWs can present as multiple growths on the anogenital skin and/or mucous membranes. They present as polymorphic, asymmetric, exophytic fronds in the areas of trauma, friction, or shaving of the anogenital area. They may also present as papular to cauliflower-like growths or as flat papular lesions (Fig. 3 ). Most patients notice the warts when they examine themselves, as generally AGWs cause little discomfort or pain. They may occasionally be pruritic or they may rarely cause local discharge

Differential diagnoses

The diagnosis of AGWs is usually clinical. Those lesions that persist, or have atypical characteristics, should be biopsied. Normal variations can be erroneously diagnosed as AGWs. Sebaceous glands, also known as Fordyce spots, are symmetrical and can be seen on the inner portion of the labia minora. They are smooth and may look like papules; sometimes sebum can be expressed from larger ones. Vestibular papillae also known as micropapillomatosis labialis are symmetrical lesions that can be seen

Treatment

External genital warts resolving time will be a median of 125 days [20]. Recommended therapies are classified as patient applied or health professional administered (Table 1).

Men more than women and younger more than older patients would prefer topical rather than destructive therapies [21]. Yet most patients choose to have treatment for their AGWs even with the knowledge that a proportion will clear spontaneously.

Prior to the HPV vaccination program, data from the nationally representative

Prevention

Condoms may not protect against AGWs as effectively as they do against other STIs [34]. Still, condom counseling should be provided as the protection against other STIs and as contraception [34].

AGWs are highly infectious. The phase 3 quadrivalent HPV vaccine randomized controlled trials showed very high efficacy in preventing AGWs in adolescents [35], young women, older women, heterosexual men, as well as men who have sex with men *[36], [37], *[38]. Reports from industrialized countries, for

Summary

AGWs are a sexually transmitted disease with considerable financial as well as psychosocial burden. There are high recurrence rates, particularly when there is immunosuppression such as concomitant HIV. Adherence to management guidelines is recommended, as condom use has limited efficacy to prevent transmission and there is no preexposure screening for HPV infection. The best preventative measure is prophylactic vaccination in young women and girls and boys prior to sexual debut which has shown

Conflict of interest

Marc Steben has received research, lecture or consultation grants from Merck, Triton and Valeant. Suzanne Marie Garland has received advisory board fees and grant support from CSL and GlaxoSmithKline, and lecture fees from Merck, GSK and Sanofi Pasteur; in addition, she has also received funding through her institution to conduct HPV vaccine studies for MSD and GSK. She is a member of the Merck Global Advisory Board as well as the Merck Scientific Advisory Committee for HPV.

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