Human papillomavirus: Difference between revisions
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===Epidemiology=== |
===Epidemiology=== |
||
+ | *Transmission is from direct contact (including during sexual encounters) or vertical (before or during birth) |
||
*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]] |
||
+ | |||
− | *Transmission is from direct contact (including during sexual encounters) or vertical (before or during birth) |
||
+ | === 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== |
==Clinical Manifestations== |
||
+ | *Incubation period [[Usual incubation period::3 to 4 months]] (range [[Incubation period range::6 weeks to 2 years]]) |
||
*Most commonly associated with warts (including genital warts), cervical cancer, and penile cancer |
*Most commonly associated with warts (including genital warts), cervical cancer, and penile cancer |
||
*Most warts resolve within 24 months without treatment |
*Most warts resolve within 24 months without treatment |
||
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| |
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|} |
|} |
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+ | |||
+ | === 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=== |
===Recurrent Respiratory Papillomatosis=== |
||
Line 82: | Line 138: | ||
**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 |
||
*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 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 |
||
+ | |||
+ | == Differential Diagnosis == |
||
+ | |||
+ | * [[Condyloma latum]] ([[secondary syphilis]]) |
||
+ | * [[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]] |
||
+ | |||
+ | == 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 |
||
+ | * 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 |
||
+ | * CO<sub>2</sub> laser therapy |
||
+ | * Previously: 5-fluorouracil (5-FU) and intralesional interferon |
||
==Prevention== |
==Prevention== |
Revision as of 22:05, 11 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
- 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
Differential Diagnosis
- Condyloma latum (secondary syphilis)
- 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
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
- 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
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, 51, 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