167: Human Papillomavirus Infections Flashcards
What is the worldwide occurrence of HPV and which populations are most affected?
HPV has a worldwide occurrence, affecting people of all ages and all races. It is most common in children and young adults.
How many genotypes of HPV exist and what are the associations of low risk and high risk types?
There are more than 150 genotypes of HPV. Low risk types cause warts, while high risk types are associated with intraepithelial neoplasia and malignancy.
What are the common characteristics of HPV lesions?
HPV lesions are well-defined, raised papules or plaques with a rough or hard surface, usually without inflammation. They are most common on the hands or feet, but can affect many skin sites, including the lower genital or oral mucosa.
What factors influence the severity and duration of HPV disease?
The severity and duration of HPV disease will depend, to a large extent, on the immune response raised against the virus infected cells.
What is the role of the E6 and E7 proteins in HPV?
The E6 and E7 proteins are pivotal to the process of viral genome amplification, which also depends on E1 and E2 proteins.
What type of cells does HPV infect and how does it enter these cells?
HPV only infects humans, specifically epithelial keratinocytes. Cell entry depends on initial adherence of the virion to the cell via heparin sulphate and a6-integrins.
What is the structure of papillomaviruses and how do new infections occur?
Papillomaviruses are DNA viruses with a nonenveloped icosahedral capsid containing double stranded genetic material as a circular genome. New infections occur when the virus particle contacts the basal epidermal keratinocyte, presumed to be via small microabrasions in the skin or mucosa.
What treatments are available for HPV infections?
Treatments for HPV infections include destructive, antiviral, antiproliferative, and immunologic modalities.
What are the characteristics of low-risk HPV types?
- Not found in malignancies or premalignancies.
- Most common in childhood and into the 20s, with 30% to 70% of school-age children having skin warts.
- Most warts in children will clear within 2 years, and only a few remain at 4 years.
What are the implications of high-risk HPV types in children?
- High-risk HPV types are found in invasive or preinvasive disease.
- Anogenital HPVs fall into the large alpha genus and maintain expression of their E6 and E7 proteins, which have oncogenic effects.
- In children, anogenital warts should raise consideration of sexual abuse.
How is HPV transmitted and what are the implications for infection control?
- Spread of infection can be via direct contact; virus particles can remain in the environment for an unknown duration.
- Protection against a new infection is via neutralizing antibodies.
- Clearance of the virus from infected individuals depends on a cell-mediated immune response.
What is the role of the L1 capsid protein in HPV vaccines?
- The anti-HPV vaccines are produced as the L1 capsid protein assembled into virus-like particles.
- These vaccines lead to a humoral response against the virus particle, providing protection against HPV infections.
What challenges do individuals with long-term immune compromise face regarding HPV?
- Individuals with long-term immune compromise, such as those with inherited immunodeficiency or transplant recipients, face significant challenges with warts and malignancy caused by HPV.
- Approximately 90% of patients five years after renal transplant have warts caused by HPV Beta types that also cause warts in healthy people.
An immunosuppressed patient presents with a history of longstanding periungual warts. What is the potential complication, and which HPV type is implicated?
The potential complication is progression to Bowen disease (full-thickness dysplasia) or invasive SCC, and HPV 16 is implicated.
What are the common sites for warts caused by HPV?
Common sites for warts are the hands and feet, especially at areas of minor trauma, such as knuckles or around nails.
What are mosaic warts and which HPV type is associated with them?
Mosaic warts are a group of small adjacent but relatively flat warts on the sole, associated with HPV 48.
What is the treatment for plane warts (Verruca plana)?
The treatment for plane warts (Verruca plana) is the immune modulator imiquimod.
What distinguishes filiform warts from other types of warts?
Filiform warts are characterized by warts on a small base with longer, fingerlike projections and are associated with HPV 4.
What are butcher’s warts and who is primarily affected?
Butcher’s warts are warts that occur in meat workers who have direct contact with wet meat, associated with HPV 7.
What is Epidermodysplasia Verruciformis and what mutations are associated with it?
Epidermodysplasia Verruciformis is a rare skin disorder associated with mild underlying primary immunodeficiency and is linked to EVER 1 and EVER 2 mutations that produce transmembrane zinc-containing proteins TMC6 and TMC8.
What are the characteristics of palmar and plantar warts?
Palmar and plantar warts (HPV 1) produce higher amounts of new particles compared to other cutaneous types and are commonly found on the palms and soles.
What type of cancer is associated with HPV 6 and 11?
Carcinoma cuniculatum or verrucous carcinoma (Buschke Lowenstein tumor) is associated with HPV 6 and 11, characterized by longstanding and slowly enlarging warty areas on soles, fingers, or anogenital skin.
What are the common HPV types associated with EV presenting as widespread flaky, scaly, or flat warty lesions?
Common HPV types associated include HPV 9, 12, 15, 19, 22-25, 36-38, 80, typically found on the face, hands, forehead, and other sun-exposed sites.
A 10-year-old child has small, flat warts on the back of their hands. What HPV type is most likely responsible, and what treatment is recommended?
The warts are likely caused by HPV 3 or 10 (plane warts). The recommended treatment is the immune modulator Imiquimod.
A meat worker develops warts on their hands after prolonged contact with wet meat. What is the specific HPV type associated with this condition?
The condition is known as Butcher’s warts, and it is associated with HPV 7.
A patient with a history of renal transplant presents with widespread flaky lesions on sun-exposed areas. What is the likely diagnosis, and which HPV types are implicated?
The likely diagnosis is Epidermodysplasia Verruciformis-like syndrome. HPV types 9, 12, 15, 19, 22-25, 36-38, and 80 are implicated.
A patient presents with longstanding, slowly enlarging warty areas on the soles. What is the likely diagnosis, and which HPV types are associated?
The likely diagnosis is Carcinoma cuniculatum or verrucous carcinoma, associated with HPV 6 and 11.
A patient presents with hyperkeratotic, hard lesions on the soles of their feet. What HPV type is most likely responsible, and what is the condition called?
The condition is called palmar and plantar warts (Myrrmecia), and it is most likely caused by HPV 1.
A patient with a history of chronic sun exposure develops skin SCC. What HPV types are commonly associated with this condition?
Skin SCC on sun-exposed skin is commonly associated with Beta HPV types, including HPV 5, 8, 14, 17, 20, 21, 47, 93, and 96.
A patient presents with a group of small, flat warts on the sole of their foot. What is the condition called, and which HPV type is responsible?
The condition is called mosaic warts, and it is caused by HPV 48.
A patient presents with benign scaly lesions on the face and hands. What is the likely diagnosis, and which HPV types are implicated?
The likely diagnosis is Epidermodysplasia Verruciformis-like syndrome, with HPV types 9, 12, 15, 19, 22-25, 36-38, and 80 implicated.
A patient presents with warts on a small base with fingerlike projections. What is the condition called, and which HPV type is responsible?
The condition is called filiform warts, and it is caused by HPV 4.
A patient presents with warts on the hands and feet. What are the most common HPV types responsible for common warts?
The most common HPV types responsible for common warts are HPV 2, 27, and 57.
A patient presents with flaky, scaly lesions on sun-exposed areas. What is the likely diagnosis, and what is the genetic mutation associated with this condition?
The likely diagnosis is Epidermodysplasia Verruciformis. The genetic mutation associated is in the EVER1 and EVER2 genes.
A patient presents with warts on the soles that produce high amounts of new viral particles. What is the condition called, and which HPV type is responsible?
The condition is called palmar and plantar warts (Myrrmecia), and it is caused by HPV 1.
A patient presents with warts on the face and hands. What is the likely diagnosis, and which HPV types are implicated?
The likely diagnosis is Epidermodysplasia Verruciformis-like syndrome, with HPV types 9, 12, 15, 19, 22-25, 36-38, and 80 implicated.
What are the common clinical features of anogenital warts caused by HPV 6 and 11?
Anogenital warts typically affect the vulva, vagina, cervix, penis, scrotum, perianal skin, and anal canal. They can present as multiple, well-defined papules or as flat or filiform lesions, often growing into larger protuberant lesions. On mucosal surfaces, they may appear macerated and pale, while on dry skin, they can be hyperkeratotic and hard. They are usually asymptomatic but can be itchy and may be traumatized with movement or sexual activity.
What is the first-line treatment for anogenital warts caused by HPV 6 and 11?
The first-line treatment for anogenital warts is topical Podophyllotoxin or Imiquimod, which has a clearance rate of 50-70%. Other treatment alternatives include topical TCA, sinecatechins from green tea, physical therapy with cryotherapy, PDT, laser, electrocautery, and surgery.
What are the potential complications of oral warts caused by HPV 6 and 11?
Oral warts can develop in the lips, oral cavity, and upper respiratory tract and are still regarded as sexually transmitted diseases (STDs). They can be flat or cauliflower-shaped and may lead to laryngeal warts, which can affect speech and breathing, especially in children infected at birth. These warts are common in individuals with HIV infection and may worsen during antiretroviral therapy.
What is the significance of the quadrivalent anti-HPV vaccine in relation to genital warts?
The quadrivalent anti-HPV vaccine, introduced in 2007, is associated with a decrease in the presentation of genital warts and the prevalence of HPV types 6 and 11, which are responsible for most anogenital warts.
What are the histological features associated with anogenital intraepithelial neoplasia and cancer caused by HPV 16?
Anogenital intraepithelial neoplasia and cancer caused by HPV 16 are characterized by dysplasia of the vulva, vagina, cervix, penis, perianal skin, and anal canal. Histological features may include bowenoid papulosis if lesions are pigmented, presenting as velvety plaques, white macerated, warty lesions, or less distinct erythematous areas. Diagnosis is confirmed through biopsy.
A 25-year-old patient presents with multiple, well-defined papules on the perianal skin. They are asymptomatic but occasionally itch. What is the most likely diagnosis, and what is the first-line treatment?
The most likely diagnosis is anogenital warts caused by HPV 6 or 11. The first-line treatment is topical Podophyllotoxin or Imiquimod, which has a 50-70% clearance rate.
A 35-year-old male presents with velvety plaques and pigmented lesions on the perianal skin. What is the differential diagnosis, and what diagnostic procedure is recommended?
The differential diagnosis includes Bowenoid papulosis and seborrheic keratosis. A biopsy is recommended for diagnosis.
A patient with HIV develops cauliflower-shaped warts in the oral cavity. What is the likely diagnosis, and which HPV types are responsible?
The likely diagnosis is oral warts, and the responsible HPV types are HPV 6 and 11.
A patient presents with acanthosis, hyperkeratosis and ballooning of keratinocytes in the upper spinous layer with small dense nuclei. What diagnostic method confirms the presence of HPV and how can it be managed?
The likely diagnosis is skin SCC. PCR is the diagnostic method that confirms the presence of Beta HPVs. Sun protection, PDT and an oral retinoid (acitretin) are useful.
A patient presents with warts on the lips and oral cavity. What is the likely diagnosis, and how is it transmitted?
The likely diagnosis is oral warts caused by HPV 6 and 11. It is transmitted sexually and is regarded as an STD.
A patient presents with warts that are macerated and pale on mucosal surfaces. What is the likely diagnosis, and what is the first-line treatment?
The likely diagnosis is anogenital warts caused by HPV 6 or 11. The first-line treatment is topical Podophyllotoxin or Imiquimod.
A patient presents with a history of HPV infection and develops metastatic skin SCC. What preventive measures could have reduced the risk?
Preventive measures include sun protection, regular surveillance for SCC, and early treatment of suspicious lesions.
What is the likely diagnosis for warts on the upper respiratory tract, and what is a common complication in childhood?
The likely diagnosis is oral warts caused by HPV 6 and 11. A common complication in childhood is laryngeal warts, which can affect speech and breathing.
What is the lifetime risk of developing cancer for an individual with Atypical Glandular Neoplasia (AGIN)?
An individual with AGIN has a 5% lifetime risk of developing cancer.
What are the clinical features associated with HPV-related Oral and Oropharyngeal Squamous Cell Carcinoma (HPV 16)?
Clinical features include silent infection with high-risk HPVs in the mouth or throat, and a stronger association with HPV infection, especially in young male patients, compared to traditional associations with smoking and alcohol.
What are the main histological findings in HPV infections?
Histological findings include acanthosis, hypergranulosis, and hyperkeratosis of the epidermis, with keratinocytes in the upper granular layer showing koilocytosis characterized by clear cytoplasm and a dense twisted nucleus.
What are the general treatment strategies for warts caused by HPV?
Treatment strategies aim to:
- Damage the infected epithelium and debulk the lesions (especially for immunocompromised patients).
- Have some effect on the virus life cycle (e.g., using Podophyllotoxin or retinoids).
- Stimulate an immune response.
What are the most commonly used destructive treatments for warts?
The most commonly used destructive treatments for warts include:
- Silver nitrate
- Phenol
- Mono- or trichloroacetic acid
- Laser or excisional surgery.
What is the most likely HPV type involved in squamous cell carcinoma in the oropharynx, and what preventive measure could reduce the incidence?
The most likely HPV type involved is HPV 16. The anti-HPV vaccine may reduce the incidence of malignancy.
What is the condition called when a patient with immunosuppression develops large areas of warts on the skin and mucous membranes?
The condition is called generalized verrucosis.
What HPV type is most likely involved in a silent infection in the oropharynx, and what are the traditional risk factors?
The most likely HPV type involved is HPV 16. Traditional risk factors include smoking and alcohol, but HPV infection is now a stronger association.
AIN (anogenital intraepithelial neoplasia) is diagnosed through biopsy, with full-thickness epidermal dysplasia (undifferentiated intraepihelial neoplasia). What is its histologic differential and how do you treat it?
Histologic differential includes:
- differentiated epidermal neoplasia (associated with chronic inflammatory genital disease such as lichen sclerosus with histologically subtler basal dysplasia, with acanthosis and hyperkeratosis, not associated with HPV infection)
The recommended treatment is surgery, if solitary; and laser or topical immunotherapy with Imiquimod for multifocal lesions.
What is the recommended preventive measure for a patient with a history of HPV infection who develops oropharyngeal SCC?
The most likely HPV type involved is HPV 16. The recommended preventive measure is the anti-HPV vaccine.
What is the recommended duration for regular treatment of warts?
Regular treatment for at least 3 months or longer is likely to be required.
What is the clearance rate for most common treatments compared to placebo?
The clearance rate for most common treatments is 60-70%, compared with 30% clearing up the placebo.
What is the most common modality of treatment for warts? Give some examples.
Destructive–It is also recommended for immunocompromised patients.
- silver nitrate
- phenol
- mono- or TCA
- laser
- excision
- salicylic acid 12-17% paint; 50% in plasters or ointment (not for the face or anogenital area)
- cryotherapy with liquid nitrogen every 3 weeks for at least 3 months (painful, not for periungual, soles, or childen)
HPV strains involves in epidermoid plantar cysts?
HPV 57 and 60.
T or F: The anti-HPV vaccine may reduce incidence of malignancy in male patients with silent oropharyngeal HPV 16 infection.
True.
