Human Papillomaviruses Flashcards
What HPV subtypes are most common in palmar/plantar warts?
HPV-1, HPV-2, HPV-4, HPV-27, HPV-57
What are the high-risk HPV subtypes?
HPV 16,18,31,33,45
16/18 are the big ones
What type of virus is HPV?
Double-stranded DNA virus
What are the major structural proteins of the HPV virus?
L1 = Major structural protein
L2= Minor structural protein
these are important for binding/entering epithelial cells
What layer of keratinocytes must HPV infect to proliferate?
The basal layer keratinocytes
What HPV proteins are responsible for DNA replication and keratinocyte immortalization?
Early proteins (E1-E7)= DNA replication + keratinocytes immortalization
What HPV proteins are responsible for virion formation?
Late protein (L1-L2): expressed in superficial epidermis and encode structural proteins required for virion formation
Which HPV proteins decrease host immune response and how do they do it?
E6 + E7 decrease host immune response (e.g., TLR9 and IL-8)
What HPV proteins are oncoproteins and how are they oncogenic?
E6+E7 in high-risk mucosal subtypes are oncoproteins
E6= ubiquitin-mediated p53 destruction –> decreased apoptosis/ increased replication/increased mutations
E7 binds Rb–> loss of inhibition of E2F transcription factor and increased expression of genes important for DNA replication
What levels of the skin have higher levels of L1 and L2 proteins and where can the complete virus be observed?
More superficial layers have higher L1 and L2 levels
- Complete virus is observed in the granular layer and above
What genus of HPV leads to most mucosal and cutaneous HPV?
Alpha genus
What cutaneous disease is the beta genus of HPV involved in?
Epidermodysplasia verruciformis
The clinical description of common warts (i.e. verruca vulgaris)?
Hyperkeratotic papules w/ pinpoint black dots (thrombosed capillaries? some discussion of this)
Most common locations for verruca vulgaris?
Fingers, dorsal hands/elbows/knees
What strains of HPV typically lead to verruca vulgaris?
HPV-1,2,4,27,57
What disease can HPV-57 be associated with?
10 nail dystrophy
What histologic findings are seen in verruca vulgaris?
- “Church spire” papillomatosis + hyperkeratosis
- Acanthosis (with elongated rete ridges)
- Hypergranulosis
- Koilocytosis (granular layer)
- Increased dermal vessels
What does it mean for a wart to be “myrmecial”?
The anthill-like appearance that some plantar warts get
What strains of HPV are associated with plantar/palmar warts?
HPV-1, 2, 4, 27, 57
What different features do plantar warts have as compared to verruca vulgaris?
Eosinophilic inclusion bodies and “ant hill” piles of keratohylain
What HPV species are associated with flat warts (verruca plana)?
HPV-3, 10, 28, 41
The clinical description of verruca plana?
Light pink/brown, soft/smooth, slightly raised, occ. Linear flat-topped papules on dorsal hands/face
Who commonly gets verruca plana?
These are more common in children; adult women>>adult men. People who shave their legs (koebnerization)
What difference can be seen on histology for verruca plana as compared to another verruca?
Less papillomatosis, mild
What are Butcher’s warts?
Extensive verruca occurring on the hands in meat/fish handlers
What is the clinical of Butcher’s warts?
Extensive verrucous papules or cauliflower-like lesions on the hands
What HPV subtypes are involved in butcher’s warts?
HPV-7, 2
What HPV subtype is associated with ridged warts?
HPV-60
Where is the pigmented form of ridged wart more common?
Japan
What is epidermodysplasia verruciformis?
Genetic disorder, Generalized polymorphic papules (generally flat wart-like appearance), on the dorsal hands, neck, face, and extremities, but also scaly pink macules or hypopigmented guttate macules/patches, and seborrheic keratosis like lesions on forehead/neck/trunk
What genes are mutated in epidermodysplasia verrcuiformis?
TMC6 (EVER1) and TMC8 (EVER2)
What HPV-subtypes are associated with epidermodysplasia verruciformis?
Genus beta HPV
-HPV-3, 5, 8, 9, 12, 14, 15, 17, 19, 25, 36, 38
What HPV subtypes are particularly important in epidermodysplasia verruciformis?
HPV type 5 and 8 because these can cause AK’s and SCC in pts w/ risk factors (>30 y/o, sun-exposed areas)
->30 will develop SCC
What group of patients is at risk of getting sporadic epidermodysplasia verruciformis-like lesions without a gene mutation?
Immunosuppressed patients
What is the histology of epidermodysplasia verruciformis?
Flat wart-like architecture + cell w/ perinuclear halos and blue-gray granular cytoplasm
What is WHIM syndrome?
AD
Warts
Hypogammaglobulinemia
Infections
Myelokathexis (neutropenia (2 /2 to myelokathexis*)
Retention of mature neutrophils in the bone marrow
What is the gene mutation in WHIM syndrome?
Primary immunodeficiency 2/2 CXCR4 mutation
What is WILD syndrome?
Warts
Immunodeficiency (cellular)
Lymphoma (primary)
Dysplasia (multifocal anogenital)
Treatments for verruca?
- Destructive: cryotherapy, ED+C, scissors/shave removal, laser (PDL or CO2)/PDT, cantharidin, and salicylic acid preparations
- Immunomodulatory/antiviral: (SADE/DPCP) and intralesional immunotherapy [e.g., Candida]
- 5-FU: (topically w/ salicylic acid usually or intralesional)
Intralesional: 5-FU, Bleomycin or cidofovir gel
What is acondyloma cuminata?
Genital warts, most common STD
- Occurs on genitals/perineum/peri-anal/groin/mons/vagina/urethra/anal canal
- Smooth, sessile, raised, skin-colored to brown lobulated papules
What HPV subtypes cause genital warts (condyloma cuminata)?
HPV-6, 11, 16, 18 and 31, HPV-33, 45
What are the high-risk subtypes of HPV?
HPV-16, 18, 31, 33, 45
HIGH YIELD QUESTION
What are the risk factors for HPV lesion progression to cancer?
HPV type (16 and 18, 31, 33-35)
Location of infection
Cigarette smoking
Uncircumcised status
Immunosuppressed status
What component of the HPV virus do the vaccines have in them?
Contain L1 major capsid protein: self-assembled into virus-like particles–> allows for development of immunity w/o any harm b/c they do not contain DNA virus
What are the 3 types of HPV vaccines?
Three types:
Quadrivalent (Gardasil; HPV-6, 11, 16, 18)
Bivalent (Cervarix; HPV 16,18)
9 valent (HPV 6, 11, 16, 18, 31, 33, 45, 52, 58)
What is bowenoid papulosis?
- Multiple brown papules/ smooth plaques
- Located on genitals/perineum/perianal
- High grade squamous intraepithelial lesions (HSIL) or SCCIS
How high of a risk is bowenoid papulosis for progression to SCC?
- High grade squamous intraepithelial lesions (HSIL) or SCCIS
- Progression to invasive SCC if very rare; a/w high-risk HPV types
What is erythroplasia of Queyrat?
- Red smooth plaque
- On glabrous penis/vulva
- HSIL or SCIS
What is the risk of progression to Eryhtroplasia of Queyrat?
Increased risk of progression to invasive SCC; has high risk HPV types (HPV-16 commonly)
What type of HPV does Erythroplasia of Queryrat and bowenoid papulosis often have?
Contain high-risk HPV types, mostly HPV-16
What is the Buschke-Lowenstein tumor?
- Arises on genitals
- Cauliflower like tumors that infiltrate deeply on external genitals and perianally
What four HPV-related cancers are in the verrucous carcinomas group?
- Buschke-Lowenstein (HPV 6, 11)
- Oral florid papillomatosis (HPV-6, 11; RFs: smoking radiation, inflammation)
- Epithelioma cuniculatum (HPV-2, 11, 16)
- Papillomatis cutis carcinoides
Histology of Buschke-Lowenstein tumor?
Papillomatous acanthotic epidermis w/ bulbous (“pushing”) downward extending rete ridges; no cellular atypia/ basement membrane penetration
What is the treatment for Buschke-Lowenstein tumor and what is the recurrence rate?
- Treatment: excision w/ clear margins
- Recurrences: frequent, has high morbidity
What patients are at higher risk of oral warts?
HIV + patients
Most common HPV subtypes in oral warts?
HPV types 6, 11
In HIV patients there may be unusual strains like 7, 71, 72, 73
What is Heck’s disease?
Focal epithelial hyperplasia
- Multiple flat wart-like papules on gingival/buccal/labial mucosa in children
common in South America
What are the most common HPV subtypes in Heck’s disease?
HPV-13, 32
What is recurrent respiratory papillomatosis?
Papillomas of the airway
- # 1 benign tumor of the larynx
- Presents with hoarseness + stridor + respiratory distress
Risk factors for recurrent respiratory papillomatosis in children and adults?
- Childhood: 2/2 to vertical transmission
- Adulthood: 2/2 genital to oral contact
HPV subtypes associated with recurrent respiratory papillomatosis?
HPV-6 , 11
Can recurrent respiratory papillomatosis progress to SCC?
Can progress to SCC, especially in smokers
What is oral florid papillomatosis?
Large exophytic verrucous tumor of oral cavity
What HPV subtypes are a/w oral florid papillomatosis?
HPV-6, 11
What percentage of warts are expected to resolve w/o treatment in 2 and 3 years?
Approximately 66% of warts will self-resolve by 2 years and 75% by 3 years