Human papillomavirus: Difference between revisions

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==Background==
  
==Background==
   
−
*Oncogenic double-stranded DNA virus in the ''Papillomaviridae'' family, with hundreds of genotypes
 +
*Oncogenic double-stranded DNA virus in the ''[[Papillomaviridae]]'' family, with hundreds of genotypes
 
*Infection with one genotype does not confer immunity to others
  
*Infection with one genotype does not confer immunity to others
   
Line 9: Line 9:
 
*Lifetime prevalence is 70% in North America
  
*Lifetime prevalence is 70% in North America
 
*HPV infection is the primary risk factor for [[cervical cancer]]
  
*HPV infection is the primary risk factor for [[cervical cancer]]
  +
**About 400 women die from [[cervical cancer]] annually
   
−
=== Risk Factors ===
 +
===Risk Factors===
   
−
==== Anogenital Lesions ====
 +
====Anogenital Lesions====
   
−
* For women:
 +
*For women:
−
** Directly related to the number of male sex partners
 +
**Directly related to the number of male sex partners
−
** Male partners' number of female sex partners
 +
**Male partners' number of female sex partners
−
** Sex with a new partner
 +
**Sex with a new partner
−
** Vaginal and anal intercourse
 +
**Vaginal and anal intercourse
−
* For men:
 +
*For men:
−
** HIV infection
 +
**HIV infection
−
** Current and past sexual behavior
 +
**Current and past sexual behavior
−
** Number of sex partners
 +
**Number of sex partners
−
** Absence of condom use
 +
**Absence of condom use
−
** Prior sexually transmitted infection
 +
**Prior sexually transmitted infection
−
** Race and ethnicity
 +
**Race and ethnicity
−
** Circumcision status
 +
**Circumcision status
   
−
=== Pathophysiology ===
 +
===Pathophysiology===
   
−
* Virus enters via a breach in the epithelium and binds to heparan proteoglycans on the basement membrane and basal cell
 +
*Virus enters via a breach in the epithelium and binds to heparan proteoglycans on the basement membrane and basal cell
−
* Replication within the basal cell, which differentiates as usual and releases virions
 +
*Replication within the basal cell, which differentiates as usual and releases virions
−
* The condyloma are formed when viral replication causes proliferation of all layers of the epidermis except for the basal cell
 +
*The condyloma are formed when viral replication causes proliferation of all layers of the epidermis except for the basal cell
−
* In high-grade lesions, viral DNA is usually integrated into the host genome, where it interferes with tumour suppression genes
 +
*In high-grade lesions, viral DNA is usually integrated into the host genome, where it interferes with tumour suppression genes
   
 
==Clinical Manifestations==
  
==Clinical Manifestations==
Line 98: Line 99:
 
|}
  
|}
   
−
=== Cutaneous Warts ===
 +
===Cutaneous Warts===
   
−
* Includes deep plantar warts, common warts, and plane warts
 +
*Includes deep plantar warts, common warts, and plane warts
−
* Usually asymptomatic, though they can bleed and cause pain
 +
*Usually asymptomatic, though they can bleed and cause pain
−
* Usually spontaneously resolve within a few months to a few years
 +
*Usually spontaneously resolve within a few months to a few years
−
* Common warts (verrucae vulgaris) are well-demarcated, exophytic, hyperkeratotic papules with a rough surface
 +
*Common warts (verrucae vulgaris) are well-demarcated, exophytic, hyperkeratotic papules with a rough surface
−
** Can occur on back of hand, between fingers, around nails (periungual), palms, soles, and (rarely) mucous membranes
 +
**Can occur on back of hand, between fingers, around nails (periungual), palms, soles, and (rarely) mucous membranes
−
** Can coalesce into larger lesions
 +
**Can coalesce into larger lesions
−
** Mosaic warts are when they coalesce into a cobblestone appearance
 +
**Mosaic warts are when they coalesce into a cobblestone appearance
−
** Filiform warts occur on the head
 +
**Filiform warts occur on the head
−
** Vegetating warts can occur on the hands of butchers, fish handlers, and meat packers
 +
**Vegetating warts can occur on the hands of butchers, fish handlers, and meat packers
−
* Plane warts (verrucae planae) are more common on children
 +
*Plane warts (verrucae planae) are more common on children
−
** Multiple, slightly elevated papules with irregular margins and smooth surface
 +
**Multiple, slightly elevated papules with irregular margins and smooth surface
−
** Can occur on face, neck, and hands
 +
**Can occur on face, neck, and hands
−
** When more elevated, they are called intermediate lesions
 +
**When more elevated, they are called intermediate lesions
−
* Plantar warts (verrucae plantaris or myrmecia) is most common in adolescents and young adults
 +
*Plantar warts (verrucae plantaris or myrmecia) is most common in adolescents and young adults
−
** When grouped in clusters, they are called mosaic warts
 +
**When grouped in clusters, they are called mosaic warts
−
** May be painful
 +
**May be painful
−
** Can also occur on the palms
 +
**Can also occur on the palms
   
−
=== Anogenital Warts ===
 +
===Anogenital Warts===
   
−
* Hyperkeratotic, exophytic papules that are either pedunculated or sessile
 +
*Hyperkeratotic, exophytic papules that are either pedunculated or sessile
−
* In men, mostly involves the cavity of the prepuce if uncircumcised, or the shaft if circumcised
 +
*In men, mostly involves the cavity of the prepuce if uncircumcised, or the shaft if circumcised
−
** Can also occur on meatus and within the distal urethra
 +
**Can also occur on meatus and within the distal urethra
−
** Very rarely involve proximal urethra or bladder
 +
**Very rarely involve proximal urethra or bladder
−
** Perianal warts are more common in men who have sex with men
 +
**Perianal warts are more common in men who have sex with men
−
* In women, they are most commonly found on the posterior introitus, the labia majora and minora, and the clitoris
 +
*In women, they are most commonly found on the posterior introitus, the labia majora and minora, and the clitoris
−
** Can also occur on the perineum, vagina, anus, cervix, and urethra
 +
**Can also occur on the perineum, vagina, anus, cervix, and urethra
   
 
===Recurrent Respiratory Papillomatosis===
  
===Recurrent Respiratory Papillomatosis===
Line 137: Line 138:
 
*In children it is caused by perinatal vertical transmission and can be life-threatening (juvenile-onset recurrent respiratory papillomatosis)
  
*In children it is caused by perinatal vertical transmission and can be life-threatening (juvenile-onset recurrent respiratory papillomatosis)
 
**25% present by 1 year, 50% by 5 years, and 100% by 11 years
  
**25% present by 1 year, 50% by 5 years, and 100% by 11 years
  +
**Occurs in 1 in 4000 live births to women with HPV infection
 
*In adults, most commonly seen in ages 20 to 40 years
  
*In adults, most commonly seen in ages 20 to 40 years
   
−
=== HIV Coinfection ===
 +
===HIV Coinfection===
   
−
* HIV infection is associated with increased risk of acquiring HPV infection
 +
*HIV infection is associated with increased risk of acquiring HPV infection
−
** Risk is decreased by HIV treatment
 +
**Risk is decreased by HIV treatment
−
* HPV infection is associated with increased risk of acquiring HIV infection
 +
*HPV infection is associated with increased risk of acquiring HIV infection
−
* Coinfection is associated with a higher risk of progression of HPV lesions
 +
*Coinfection is associated with a higher risk of progression of HPV lesions
   
  +
=== Infection in Children ===
−
== Differential Diagnosis ==
  
   
  +
* Genital warts can be acquired from contact with warts on caregivers' hands or on childrens' own hands
−
* [[Condyloma latum]] ([[secondary syphilis]])
  
  +
* Vertical transmission can also occur
−
* [[Seborrheic keratosis]], localized hyperpigmented lesions that are rarely associated with malignancy
  
−
* [[Molluscum contagiosum]], caused by a poxvirus, highly infectious, and common in immunodeficiency; lesions are usually umbilicated
  
−
* [[Pearly penile papules]], angiofibromas that occur at the penile corona and are normal variants
  
−
* [[Neoplasm]]
  
−
** [[Bowen disease]], ''in situ'' squamous cell carcinoma confined to the epidermis and can occasionally become invasive
  
−
** [[Bowenoid papulosis]]
  
−
** [[Squamous cell carcinoma]]
  
−
** [[Buschke-Lowenstein tumor]], a rare and highly differentiated genital carcinoma
  
−
** [[Vulvar intraepithelial neoplasia]]
  
−
** [[Benign nevus]]
  
−
** [[Dysplastic nevus]]
  
   
  +
=== Associated Malignancies ===
−
== Diagnosis ==
  
   
  +
* HPV is the underlying cause of:
−
* Cutaneous and anogenital warts are usually diagnosed clinically
  
  +
** Almost 100% of cervical cancer
−
* For cervical and rectal lesions, soaking with 3 to 5% acetic acid for 3 to 5 minutes followed by colposcopy improves diagnosis of those lesions
  
  +
** 50% of vulvar and penile cancer
−
** Acetic acid will cause whitening of the lesions
  
  +
** Over 90% of anal cancer
  +
* Also contributes to oropharyngeal and nasopharyngeal cancers
   
  +
==Differential Diagnosis==
−
=== Cervical Cytology ===
  
   
  +
*[[Condyloma latum]] ([[secondary syphilis]])
−
* Cervical cytology with Papanicolaou testing
  
  +
*[[Seborrheic keratosis]], localized hyperpigmented lesions that are rarely associated with malignancy
−
* Uses ASCCP system to describe grade
  
  +
*[[Molluscum contagiosum]], caused by a poxvirus, highly infectious, and common in immunodeficiency; lesions are usually umbilicated
−
** Atypical squamous cells of undetermined significance (ASCUS)
  
  +
*[[Pearly penile papules]], angiofibromas that occur at the penile corona and are normal variants
−
** Atypical squamous cells for which a high-grade squamous intraepithelial lesion cannot be excluded (ASCH)
  
  +
*[[Dermatitis]]
−
** Low-grade squamous intraepithelial lesion (LSIL)
  
  +
*[[Neoplasm]]
−
*** Includes koilocytic or condulomatous atypia, mild dysplasia, and cervical intraepithelial neoplasia (CIN) 1
  
  +
**[[Bowen disease]], ''in situ'' squamous cell carcinoma confined to the epidermis and can occasionally become invasive
−
** High-grade squamous intraepithelial lesion (HSIL)
  
  +
**[[Bowenoid papulosis]]
−
*** Includes moderate and severe dysplasia, CIN 2, CIN 3, and carcinoma in situ (CIS)
  
−
** [[Squamous cell carcinoma]]
 +
**[[Squamous cell carcinoma]]
  +
**[[Buschke-Lowenstein tumor]], a rare and highly differentiated genital carcinoma
  +
**[[Vulvar intraepithelial neoplasia]]
  +
**[[Benign nevus]]
  +
**[[Dysplastic nevus]]
   
−
== Management ==
 +
==Diagnosis==
   
  +
*Cutaneous and anogenital warts are usually diagnosed clinically
−
=== Cutaneous Warts ===
  
  +
*For cervical and rectal lesions, soaking with 3 to 5% acetic acid for 3 to 5 minutes followed by colposcopy improves diagnosis of those lesions
  +
**Acetic acid will cause whitening of the lesions
   
  +
===Cervical Cytology===
−
* Since many lesions will spontaneously resolve, can watch and wait
  
−
* Most common treatment is topical [[salicylic acid]], often sold over-the-counter and applied daily for up to 12 weeks
  
−
** Before applying treatment, need to do hot water soak and abrasion in order to remove the cornified layer
  
−
* Another common treatment is cryotherapy with topical liquid nitrogen
  
−
** Most effective with a sustained 10 second freeze, which can cause pain and blisters
  
−
** Frequently needs multiple treatments, spaced every 2 weeks
  
−
* Another treatment is occlusive duct tape application (occlusive therapy)
  
−
* Less evidence for glutaraldehyde, formaldehyde, podofilox, and cantharidin
  
   
  +
*Cervical cytology with Papanicolaou testing
−
=== Anogenital Warts ===
  
  +
*Uses ASCCP system to describe grade
  +
**Atypical squamous cells of undetermined significance (ASCUS)
  +
**Atypical squamous cells for which a high-grade squamous intraepithelial lesion cannot be excluded (ASCH)
  +
**Low-grade squamous intraepithelial lesion (LSIL)
  +
***Includes koilocytic or condulomatous atypia, mild dysplasia, and cervical intraepithelial neoplasia (CIN) 1
  +
**High-grade squamous intraepithelial lesion (HSIL)
  +
***Includes moderate and severe dysplasia, CIN 2, CIN 3, and carcinoma in situ (CIS)
  +
**[[Squamous cell carcinoma]]
   
  +
==Management==
−
* 10 to 20% will spontaneously resolve within 3 to 4 months
  
  +
−
* No great evidence in favour of any specific treatment
  
  +
===Cutaneous Warts===
−
* Cryotherapy, as for cutaneous lesions, applied every 1 to 2 weeks
  
  +
−
** Very effective, and safe in pregnancy
  
  +
*Since many lesions will spontaneously resolve, can watch and wait
−
* [[Podofilox]] (podophyllotoxin) 0.5% solution applied twice daily for 3 days followed by 4 days off, for up to 4 weeks
  
  +
*Most common treatment is topical [[salicylic acid]], often sold over-the-counter and applied daily for up to 12 weeks
−
** Plant extract that is a mitotic poison but unclear mechanism of action against HPV
  
  +
**Before applying treatment, need to do hot water soak and abrasion in order to remove the cornified layer
−
** Causes chemical burns in many patients, but better tolerated than podophyllin
  
  +
*Another common treatment is [[cryotherapy]] with topical liquid nitrogen
−
** Contraindicated in pregnancy
  
  +
**Most effective with a sustained 10 second freeze, which can cause pain and blisters
−
** Relapses are common
  
  +
**Frequently needs multiple treatments, spaced every 2 weeks
−
* [[Imiquimod]] 5% cream applied once daily, for 5 days each week, for up to 16 weeks
  
  +
*Another treatment is occlusive duct tape application (occlusive therapy)
−
** Binds to and activates TLR7 ± TLR8
  
  +
*Less evidence for [[glutaraldehyde]], [[formaldehyde]], [[podofilox]], and [[cantharidin]]
−
** Causes itching/burning, erythema, erosions, and swelling
  
  +
−
** Relapses are common
  
  +
===Anogenital Warts===
−
* Veregen 15% ointment applied three times daily for up to 16 weeks
  
  +
−
** Green tea extract that contains a number of possibly active ingredients
  
  +
*10 to 20% will spontaneously resolve within 3 to 4 months
−
** Causes local erythema, pruritus, pain, and ulceration
  
  +
*Up to 90% will clear them by 2 years
−
* Trichloroacetic acid 10 to 90% solution applied weekly
  
  +
*No great evidence in favour of any specific treatment
−
** Causes ulcers
  
  +
*[[Cryotherapy]], as for cutaneous lesions, applied every 1 to 2 weeks
−
** Safe in pregnancy
  
  +
**Very effective, and safe in pregnancy
−
* Surgical or electrosurgical resection
  
  +
*[[Podofilox]] (podophyllotoxin) 0.5% solution applied twice daily for 3 days followed by 4 days off, for up to 4 weeks
−
** May result in scarring
  
  +
**Plant extract that is a mitotic poison but unclear mechanism of action against HPV
−
* CO<sub>2</sub> laser therapy
  
  +
**Causes chemical burns in many patients, but better tolerated than podophyllin
−
* Previously: 5-fluorouracil (5-FU) and intralesional interferon
  
  +
**Contraindicated in pregnancy
  +
**Relapses are common
  +
*[[Imiquimod]] 5% cream applied once daily, for 5 days each week, for up to 16 weeks
  +
**Binds to and activates TLR7 ± TLR8
  +
**Causes itching/burning, erythema, erosions, and swelling
  +
**Relapses are common
  +
*[[Veregen]] 15% ointment applied three times daily for up to 16 weeks
  +
**Green tea extract that contains a number of possibly active ingredients
  +
**Causes local erythema, pruritus, pain, and ulceration
  +
*[[Trichloroacetic acid]] 10 to 90% solution applied weekly
  +
**Causes ulcers
  +
**Safe in pregnancy
  +
*Surgical or electrosurgical resection
  +
**May result in scarring
  +
*CO<sub>2</sub> laser therapy
  +
*Previously: [[5-fluorouracil]] (5-FU) and intralesional [[interferon]]
   
 
==Prevention==
  
==Prevention==
   
 
===Vaccination===
  
===Vaccination===
  +
  +
* Uses viral-like particles that express L1 capsid protein with aluminum as an adjuvant
  +
 
{| class="wikitable"
  
{| class="wikitable"
 
! rowspan="3" |Vaccine
  
! rowspan="3" |Vaccine
Line 250: Line 270:
 
|-
  
|-
 
|Gardasil-9
  
|Gardasil-9
−
|6, 11, 16, 18, 31, 33, 45, 51, 58
 +
|6, 11, 16, 18, 31, 33, 45, 52, 58
 
|}
  
|}
   
Line 261: Line 281:
 
**HPV-4: given at 0, 2, and 6 months
  
**HPV-4: given at 0, 2, and 6 months
 
**HPV-9: given at 0, 2, and 6 months
  
**HPV-9: given at 0, 2, and 6 months
  +
*Vaccination with quadravalent vaccine covers about 70% of cervical cancer genotypes, and the nonavalent about 65%
  +
*Vaccination of genotypes 6 and 11 cover about 90% of genital warts
  +
*Not recommended in pregnancy, but does not appear to be harmful
   
 
[[Category:DNA viruses]]
  
[[Category:DNA viruses]]

Revision as of 10:54, 12 November 2020

Background

  • Oncogenic double-stranded DNA virus in the Papillomaviridae family, with hundreds of genotypes
  • Infection with one genotype does not confer immunity to others

Epidemiology

  • Transmission is from direct contact (including during sexual encounters) or vertical (before or during birth)
  • Lifetime prevalence is 70% in North America
  • HPV infection is the primary risk factor for cervical cancer

Risk Factors

Anogenital Lesions

  • For women:
    • Directly related to the number of male sex partners
    • Male partners' number of female sex partners
    • Sex with a new partner
    • Vaginal and anal intercourse
  • For men:
    • HIV infection
    • Current and past sexual behavior
    • Number of sex partners
    • Absence of condom use
    • Prior sexually transmitted infection
    • Race and ethnicity
    • Circumcision status

Pathophysiology

  • Virus enters via a breach in the epithelium and binds to heparan proteoglycans on the basement membrane and basal cell
  • Replication within the basal cell, which differentiates as usual and releases virions
  • The condyloma are formed when viral replication causes proliferation of all layers of the epidermis except for the basal cell
  • In high-grade lesions, viral DNA is usually integrated into the host genome, where it interferes with tumour suppression genes

Clinical Manifestations

  • Incubation period 3 to 4 months (range 6 weeks to 2 years)
  • Most commonly associated with warts (including genital warts), cervical cancer, and penile cancer
  • Most warts resolve within 24 months without treatment
Disease Common Genotypes Uncommon Genotypes
Plantar warts 1, 2, 27 4, 26, 28, 29, 41, 57, 63, 65, 77, 117, 125, 128, 129, 130, 131, 132, 133, 148, 149, 179, 184
Common warts 1, 2, 4, 27
Warts of meat, poultry, and fish handlers 2, 7 1, 3, 4, 10, 28
Flat and intermediate warts 3, 10 27, 28, 38, 41, 49, 75, 76, 126
Epidermodysplasia verruciformis 5, 8, 9, 12, 14, 15, 17 19, 20, 21, 22, 23, 24, 25, 36, 37, 38, 47, 49, 50, 75, 93
Condylomata acuminata 6, 11 16, 18, 26, 31, 33, 35, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 58, 59, 66, 68, 70, 153, 175, 178, 180, 200, 201, 202
Intraepithelial neoplasia (unspecified) 26, 30, 34, 39, 40, 53, 57, 59, 61, 62, 67, 68, 69, 71, 81, 83
Intraepithelial neoplasia (low-grade) 6, 11 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, 54, 61, 70, 72, 74
Intraepithelial neoplasia (high-grade) 16, 18 6, 11, 31, 33, 34, 35, 39, 42, 44, 45, 51, 52, 56, 58, 66, 67
Cervical carcinoma 16, 18 26, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 67, 68, 73, 82
Recurrent respiratory papillomatosis 6, 11 16, 18, 31, 33, 35, 39
Focal epithelial hyperplasia of Heck 13, 32 18, 33, 45
Conjunctival papillomas and carcinomas 6, 11, 16

Cutaneous Warts

  • Includes deep plantar warts, common warts, and plane warts
  • Usually asymptomatic, though they can bleed and cause pain
  • Usually spontaneously resolve within a few months to a few years
  • Common warts (verrucae vulgaris) are well-demarcated, exophytic, hyperkeratotic papules with a rough surface
    • Can occur on back of hand, between fingers, around nails (periungual), palms, soles, and (rarely) mucous membranes
    • Can coalesce into larger lesions
    • Mosaic warts are when they coalesce into a cobblestone appearance
    • Filiform warts occur on the head
    • Vegetating warts can occur on the hands of butchers, fish handlers, and meat packers
  • Plane warts (verrucae planae) are more common on children
    • Multiple, slightly elevated papules with irregular margins and smooth surface
    • Can occur on face, neck, and hands
    • When more elevated, they are called intermediate lesions
  • Plantar warts (verrucae plantaris or myrmecia) is most common in adolescents and young adults
    • When grouped in clusters, they are called mosaic warts
    • May be painful
    • Can also occur on the palms

Anogenital Warts

  • Hyperkeratotic, exophytic papules that are either pedunculated or sessile
  • In men, mostly involves the cavity of the prepuce if uncircumcised, or the shaft if circumcised
    • Can also occur on meatus and within the distal urethra
    • Very rarely involve proximal urethra or bladder
    • Perianal warts are more common in men who have sex with men
  • In women, they are most commonly found on the posterior introitus, the labia majora and minora, and the clitoris
    • Can also occur on the perineum, vagina, anus, cervix, and urethra

Recurrent Respiratory Papillomatosis

  • Papillomas appear most commonly in larynx, but also trachea, bronchi, and lungs
    • Hoarseness, dysphonia, airway obstruction, respiratory distress, and stridor
    • In lungs, can cause nodules, atelectasis, and secondary bacterial pneumonia, with eventual bronchiectasis and vacitation
    • Can progress to invasive squamous papillomatosis or even squamous cell carcinoma
  • Genotypes 6 and 11 most commonly implicated
  • In children it is caused by perinatal vertical transmission and can be life-threatening (juvenile-onset recurrent respiratory papillomatosis)
    • 25% present by 1 year, 50% by 5 years, and 100% by 11 years
    • Occurs in 1 in 4000 live births to women with HPV infection
  • In adults, most commonly seen in ages 20 to 40 years

HIV Coinfection

  • HIV infection is associated with increased risk of acquiring HPV infection
    • Risk is decreased by HIV treatment
  • HPV infection is associated with increased risk of acquiring HIV infection
  • Coinfection is associated with a higher risk of progression of HPV lesions

Infection in Children

  • Genital warts can be acquired from contact with warts on caregivers' hands or on childrens' own hands
  • Vertical transmission can also occur

Associated Malignancies

  • HPV is the underlying cause of:
    • Almost 100% of cervical cancer
    • 50% of vulvar and penile cancer
    • Over 90% of anal cancer
  • Also contributes to oropharyngeal and nasopharyngeal cancers

Differential Diagnosis

Diagnosis

  • Cutaneous and anogenital warts are usually diagnosed clinically
  • For cervical and rectal lesions, soaking with 3 to 5% acetic acid for 3 to 5 minutes followed by colposcopy improves diagnosis of those lesions
    • Acetic acid will cause whitening of the lesions

Cervical Cytology

  • Cervical cytology with Papanicolaou testing
  • Uses ASCCP system to describe grade
    • Atypical squamous cells of undetermined significance (ASCUS)
    • Atypical squamous cells for which a high-grade squamous intraepithelial lesion cannot be excluded (ASCH)
    • Low-grade squamous intraepithelial lesion (LSIL)
      • Includes koilocytic or condulomatous atypia, mild dysplasia, and cervical intraepithelial neoplasia (CIN) 1
    • High-grade squamous intraepithelial lesion (HSIL)
      • Includes moderate and severe dysplasia, CIN 2, CIN 3, and carcinoma in situ (CIS)
    • Squamous cell carcinoma

Management

Cutaneous Warts

  • Since many lesions will spontaneously resolve, can watch and wait
  • Most common treatment is topical salicylic acid, often sold over-the-counter and applied daily for up to 12 weeks
    • Before applying treatment, need to do hot water soak and abrasion in order to remove the cornified layer
  • Another common treatment is cryotherapy with topical liquid nitrogen
    • Most effective with a sustained 10 second freeze, which can cause pain and blisters
    • Frequently needs multiple treatments, spaced every 2 weeks
  • Another treatment is occlusive duct tape application (occlusive therapy)
  • Less evidence for glutaraldehyde, formaldehyde, podofilox, and cantharidin

Anogenital Warts

  • 10 to 20% will spontaneously resolve within 3 to 4 months
  • Up to 90% will clear them by 2 years
  • No great evidence in favour of any specific treatment
  • Cryotherapy, as for cutaneous lesions, applied every 1 to 2 weeks
    • Very effective, and safe in pregnancy
  • Podofilox (podophyllotoxin) 0.5% solution applied twice daily for 3 days followed by 4 days off, for up to 4 weeks
    • Plant extract that is a mitotic poison but unclear mechanism of action against HPV
    • Causes chemical burns in many patients, but better tolerated than podophyllin
    • Contraindicated in pregnancy
    • Relapses are common
  • Imiquimod 5% cream applied once daily, for 5 days each week, for up to 16 weeks
    • Binds to and activates TLR7 ± TLR8
    • Causes itching/burning, erythema, erosions, and swelling
    • Relapses are common
  • Veregen 15% ointment applied three times daily for up to 16 weeks
    • Green tea extract that contains a number of possibly active ingredients
    • Causes local erythema, pruritus, pain, and ulceration
  • Trichloroacetic acid 10 to 90% solution applied weekly
    • Causes ulcers
    • Safe in pregnancy
  • Surgical or electrosurgical resection
    • May result in scarring
  • CO2 laser therapy
  • Previously: 5-fluorouracil (5-FU) and intralesional interferon

Prevention

Vaccination

  • Uses viral-like particles that express L1 capsid protein with aluminum as an adjuvant
Vaccine Genotypes Schedule
Girls and Women Boys and Men
9 to 15 years ≥15 years Immunocompromised 9 to 15 years ≥15 years Immunocompromised
Cervarix 16, 18 2 or 3 dose 3 dose 3 dose not indicated
Gardasil 6, 11, 16, 18 2 or 3 dose 3 dose 3 dose
Gardasil-9 6, 11, 16, 18, 31, 33, 45, 52, 58
  • Two-dose schedule
    • Only indicated for children aged at least 9 to less than 15 years
    • Given at 0 and 6 months
  • Three-dose schedule
    • Indicated for everyone, including children 9 years and older, men and women 15 years and older and immunocompromised people
    • HPV-2: given at 0, 1, and 6 months
    • HPV-4: given at 0, 2, and 6 months
    • HPV-9: given at 0, 2, and 6 months
  • Vaccination with quadravalent vaccine covers about 70% of cervical cancer genotypes, and the nonavalent about 65%
  • Vaccination of genotypes 6 and 11 cover about 90% of genital warts
  • Not recommended in pregnancy, but does not appear to be harmful
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