Human Papillomavirus (HPV) and Genital Warts

Table of contents
Article 🔍
A comprehensive topic overview

Introduction

Human papillomavirus (HPV) is a non-enveloped double-stranded circular DNA virus in the P a p i l l o m a v i r i d a e family. There
are over 150 types of HPV, 40 of which a
1
Important low-risk types include HPV-6 and HPV-11, which cause genital warts, the most common viral sexually
transmitted infection (STI).
1
Worldwide, high-risk HPV causes around 5% of cancers, a
2
This article will focus on the mechanism of HPV infection, and the pathophysiology, clinical features, and management of
genital warts. For more information on the closely linked cervical cancer and anal cancer, please read their respective
articles.
Epidemiology
HPV is extremely prevalent. Nearly all sexually active men and women acquire HPV infection during their lifetime, and
almost 40% of women are infected with HPV within the
3,4
All HPV types can cause proliferative lesions, however, the most prevalent types are classi
malignant neoplasms, and low-risk if they can cause benign lesions, such as genital warts.
Low-risk HPV-6 and HPV-11 are the most common causes of genital warts, which is the most common viral STI diagnosed
in sexual health clinics in the UK and worldwide. In 2019, there were 50,700 diagnoses of the
This was almost halved to 27, 473 in 2020; this decline is thought to be related to the expanded HPV vaccine programme
and the reduction in face-to-face consultations owing to the COVID-19 pandemic.
5
High-risk HPV causes around 5% of cancers worldwide and the prevalence of high-risk HPV in the UK is 16%, including the
most common type- HPV-16 (12%). 6
Through the mechanisms described below, HPV can cause cancer of the cervix, vulva,
vagina, anus, penis, head, and neck (Figure 1).
Figure 1. Number of new diagnoses
(blue) and mortality (red) for HPV-related
cancers for men (right) and women (left).
Based upon data collected in the United
Kingdom and Northern Ireland in 2019.
2Aetiology
HPV belongs to the P a p i l l o m a v i r i d a e family and includes over 200 di
genome. Although all HPV types can cause proliferative lesions, the most prevalent types are classi
low-risk according to their risk of causing malignant neoplasms or benign lesions, such as genital warts.
Important high-risk types include HPV-16 and HPV-18, which contribute to over 70% of cervical cancer, and 31, 33, 35, 45, 52
and 58, which account for an additional 20% of cervical cancers. Low-risk HPV capable of causing genital warts include
HPV-6 and HPV-11.
1
HPV life cycle
Microtrauma to the epithelial cells of the skin, oral and genital mucosa provides the virus access to basal keratinocytes.
HPV uses its L1 and L2 capsid proteins to bind and enter the cell via endocytosis.
1
The undi
establishes a persistent infection, or asymmetrically, whereby one daughter cell moves up through epithelium. As these
infected basal cells di
and produce new virions to be released from the di
7
The majority (70-90%) of HPV infections are asymptomatic and are cleared within 12-14 months by the immune system via
a Th1 pro-in
1
This immune response may be su
numbers which avoid detection. However, only 70-80% of genital HPV infection results in antibody production, which is
insu
1
Pathophysiology and carcinogenesis
HPV employs several strategies to induce hyperproliferation of the infected epithelia, resulting in warts\:
8
Genital warts\: verrucous papules in the anogenital area
Common warts\: rough, raised bumps commonly on the hands and
Plantar warts (verrucas)\: hard, grainy growth commonly on the heels or balls of feet
Flat warts\:
High-risk HPV types can remain intraepithelial by proliferating through the undi
the host immune response. These oncogenic types demonstrate increased activity of viral E6 and E7 oncoproteins, which
respectively inhibit p53 and pRb tumour suppressor genes. This results in cell cycle dysregulation, uncontrolled cellular
proliferation and the accumulation of mutations that can lead to invasive malignancy.
1
Transmission9
HPV most commonly spreads through direct skin-skin contact during sexual intercourse.
Other routes of transmission include\:
Contact with contaminated surfaces or objects
Oro-genital transmission
Perinatal vertical transmission
Autoinoculation

Risk factors

Factors increasing the risk of HPV include\:
Early age of
A high number of sexual partners
Condomless sex
Immunosuppression (including HIV)Clinical features
History
Most HPV infections (70-90%), are asymptomatic and are cleared within 12-14 months by the immune system.
Warts tend to present as single or multiple 2-5mm cauli
non-keratinised, whereas, on hairy skin, these tend to be
Warts may be associated with the following symptoms\:
Pruritus and irritation
Pain and bleeding due to local trauma
Haematuria and distortion of urinary
A full sexual history should be taken to assess relevant risk factors. This should include HPV vaccination history, sexual
activity, number of sexual partners, use of barrier contraception, and symptoms suggesting co-infection with a sexually
transmitted infection.
Clinical examination
It is important to examine the anogenital area, including the external genitalia, perineum, and anus to visually con
diagnosis and determine the extent of the lesions. Other examinations required may include\:
Vaginal speculum examination
Meatoscopy for intra-meatal warts
Proctoscopy for warts at the anal margin
Anoscopy is recommended in patients with recurrent perianal warts
Figure 2. Penile warts.
10Figure 3. Perianal warts.
11
Figure 4. Extensive warts around the labia and perianal region.
12

Di

Table 1. Di
Di
diagnosis
Clinical summary
Condyloma latum
Moist whiteish papules which may secrete
Highly contagious manifestation of secondary syphilis
Systemic symptoms may include fever, malaise, weight
lossMolluscum
contagiosum
Pearly penile
papules
Skin tags
Carcinoma in situ
Fleshy or pearl-coloured lesions with central dells
(Figure 5)
Caused by the molluscum contagiosum virus (P o x v i r u s )
1-2mm
sulcus of the penis glans (Figure 6)
Asymptomatic, normal anatomical variant
Soft, skin-coloured or tan-brown, round/oval,
pedunculated papilloma
Usually found on the neck, armpits, around the groin or
under breasts
Multifocal, erythematous or pigmented lesions
Usually have a smooth and velvety surface
Figure 5. Molluscum contagiosum.
13Figure 6. Pearly penile papules.
14

Investigations

Genital warts are diagnosed following clinical examination. Swabs and blood tests are not routinely performed. However, it
is important to o
At the bedside, this may include a urine sample and swabs of the vagina, cervix, rectum and oropharynx for NAAT
(chlamydia, gonorrhoea). Laboratory investigations may include full blood count, CRP and serology (HIV, syphilis, HBV,
HCV).
Biopsy could be considered if the wart is indurated,
9

Management

Although there is no speci
and lesions. However, in around 20% of people, warts disappear within 6 months and require no treatment.
Treatment should be led by a sexual health specialist but can be performed in primary care. Options should be discussed
and the patient’s preference for self-administration should be considered.
Self-administered treatment includes topical treatment with podophyllotoxin, imiquimod and sinecathins. Those receiving
these treatments should be advised of potential side e
sexual partner. Imiquimod and sinecatechins can also weaken condoms and make them less e
with trichloroacetic acid, or use ablative methods such as cryotherapy, excision or electrocautery.Patient advice
All patients should be counselled regarding smoking cessation and using barrier methods of contraception. Consider
suggesting that sexual partners may beneother STIs.
Patients may require reassurance that due to the long latency of HPV (3 weeks – 8 months), a recent diagnosis does not
always imply partner in
Prevention
and vaccination.
Protective factors against HPV infection include condom usage, male circumcision, limiting the number of sexual partners
Vaccination15,16
HPV vaccines contain particles from the major protein of the viral capsid. There have been several changes to the
vaccination schedule, but currently, the following groups are eligible\:
Girls and boys aged 11-14\: 2 doses, one given 6-24 months after the
Individuals aged 15-25 who did not receive it\: 2 doses, 6 months apart
Men-who-have-sex-with-men (MSM) aged 15-45\: 2 doses, 6 months apart
High-risk individuals (transgender, sex workers)\: 2 doses, 6 months apart
People living with HIV (PLWH)\: 3 doses, all within 24 months
In 2008, the bivalent vaccine against HPV 16 and 18 was introduced in the national immunisation programme, however, this
was replaced in 2012 by the quadrivalent vaccine Gardasil (against HPV 6, 11, 16 and 18). This is planned to be replaced
again in 2022 by the 9-valent vaccine Gardasil 9 (against HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58) to o
against cancer and genital warts.
The programme was initially aimed to provide protection for young girls before the onset of sexual activity but was
expanded in 2019 to include boys. As of 2020, there is 85% coverage for girls and 53% for boys.
For individuals aged 15-25 who did not receive the vaccine, MSM aged 15-45 and high-risk groups between the ages of 15-
25 are eligible for the vaccine, a schedule of 3 doses within 12 months was recommended, however from April 2022, has
changed to 2 doses, 6 months apart.

Complications

The main complications result from anxiety and distress relating to the appearance of warts.
Topical treatments may result in persistent hypo- or hyper-pigmentation and hypertrophic scarring.
Prognosis
In around 20% of people, warts disappear within 6 months, requiring no treatment.

Key points

Human papillomavirus (HPV) is a DNA virus that infects the basal epithelium of the skin and oral and genital mucosa
HPV is extremely prevalent and acquired by nearly all sexually active adults during their lifetime
HPV is most commonly transmitted through sexual intercourse
Important risk factors include early sexual intercourse, a high number of sexual partners, condomless sex, HIV infection
and immunosuppression
Most HPV infections are asymptomatic and cleared by the immune system within 2 years
High-risk HPV include HPV 16 and HPV 18, which cause cancers such as cervical cancer
Low-risk HPV includes HPV 6 and HPV 11, which can cause genital warts
Genital warts are often asymptomatic but may cause pruritus, bleeding, pain and urinary symptoms
Warts disappear within 6 months in 20% of cases, but treatment can be topical or ablative
HPV can be prevented by vaccination, which is o
individuals, sex workers, and people living with HIVReferences
de Sanjose, S., Brotons, M. and Pavon, M.A., 2018. The natural history of human papillomavirus infection. B e s t p r a c t i c e &
r e s e a r c h C l i n i c a l o b s t e t r i c s & g y n a e c o l o gy , 4 7 , pp.2-13.
Bruni L, Albero G, Serrano B, Mena M, Collado JJ, Gómez D, Muñoz J, Bosch FX, de Sanjosé S. ICO/IARC Information Centre

Related notes

on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in United Kingdom of Great
Britain and Northern Ireland. Summary Report 22 October 2021.
Centre for Disease Control, 2022. H P V Available at [LINK]
Chickenpox (VZV)
Clostridioides di
Public Health England, 2014. Human papillomavirus (HPV)\: the green book, chapter 18a.
COVID-19
Public Health England, 2019. Sexually transmitted infections and screening for chlamydia in England. H e a l t h P r o t e c t i o n
R e p o r t , 1 3 (19), Dengue Fever
pp.1-38.
Sonnenberg, P., Tanton, C., Mesher, D., King, E., Beddows, S., Field, N., Mercer, C.H., Soldan, K. and Johnson, A.M., 2019.
Human Immunode
Epidemiology of genital warts in the British population\: implications for HPV vaccination programmes. Sexually transmitted
infections, 95(5), pp.386-390.

Test yourself

Roden, R.B. and Stern, P.L., 2018. Opportunities and challenges for human papillomavirus vaccination in cancer. N a t u r e
R e v i e w s C a n c e r , 1 8 (4), pp.240-254.
Mammas, I.N., Sourvinos, G. and Spandidos, D.A., 2009. Human papilloma virus (HPV) infection in children and
adolescents. Contents
E u r o p e a n j o u r n a l o f p e d i a t r i c s , 1 6 8 (3), pp.267-273.
National Institute for Health and Care Excellence, 2017. W a r t s – a n o g e n i t a l . Available at [LINK]
Introduction
Jmarchn. Penile warts in the foreskin. License\: [CC BY-SA]
CDC Public Health Image Library. 16733. License\: [Public domain]
Aetiology
CDC Public Health Image Library. 16734. License\: [Public domain]
Dave Bray, MD. Close-up view of typical molluscum bumps. License\: [Public domain]
Risk factors
AndyRich48. Pearly Penile Papules. License\: [CC BY-SA]
Clinical features
Joint Formulary Committee. British National Formulary (online) London\: BMJ Group and Pharmaceutical Press, 2022. H u m a n
p a p i l l o m a v i r u s v a c c i n e . Available at [LINK]
Di
NHS England. GOV.UK. 2022. H P V i m m u n i s a t i o n p r o g r a m m e \: c h a n ge s f r o m A p r i l 2 0 2 2 l e t t e r . [online] Available at [LINK]
Investigations

Reviewer

Management
Source\: geekymedics.com