167: Human Papillomavirus Infections

Question 1

What is the worldwide occurrence of HPV and which populations are most affected?

Answer 1

HPV has a worldwide occurrence, affecting people of all ages and all races. It is most common in children and young adults.

Question 2

How many genotypes of HPV exist and what are the associations of low risk and high risk types?

Answer 2

There are more than 150 genotypes of HPV. Low risk types cause warts, while high risk types are associated with intraepithelial neoplasia and malignancy.

Question 3

What are the common characteristics of HPV lesions?

Answer 3

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.

Question 4

What factors influence the severity and duration of HPV disease?

Answer 4

The severity and duration of HPV disease will depend, to a large extent, on the immune response raised against the virus infected cells.

Question 5

What is the role of the E6 and E7 proteins in HPV?

Answer 5

The E6 and E7 proteins are pivotal to the process of viral genome amplification, which also depends on E1 and E2 proteins.

Question 6

What type of cells does HPV infect and how does it enter these cells?

Answer 6

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.

Question 7

What is the structure of papillomaviruses and how do new infections occur?

Answer 7

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.

Question 8

What treatments are available for HPV infections?

Answer 8

Treatments for HPV infections include destructive, antiviral, antiproliferative, and immunologic modalities.

Question 9

What are the characteristics of low-risk HPV types?

Answer 9

• 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.

Question 10

What are the implications of high-risk HPV types in children?

Answer 10

• 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.

Question 11

How is HPV transmitted and what are the implications for infection control?

Answer 11

• 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.

Question 12

What is the role of the L1 capsid protein in HPV vaccines?

Answer 12

• 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.

Question 13

What challenges do individuals with long-term immune compromise face regarding HPV?

Answer 13

• 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.

Question 14

An immunosuppressed patient presents with a history of longstanding periungual warts. What is the potential complication, and which HPV type is implicated?

Answer 14

The potential complication is progression to Bowen disease (full-thickness dysplasia) or invasive SCC, and HPV 16 is implicated.

Question 15

What are the common sites for warts caused by HPV?

Answer 15

Common sites for warts are the hands and feet, especially at areas of minor trauma, such as knuckles or around nails.

Question 16

What are mosaic warts and which HPV type is associated with them?

Answer 16

Mosaic warts are a group of small adjacent but relatively flat warts on the sole, associated with HPV 48.

Question 17

What is the treatment for plane warts (Verruca plana)?

Answer 17

The treatment for plane warts (Verruca plana) is the immune modulator imiquimod.

Question 18

What distinguishes filiform warts from other types of warts?

Answer 18

Filiform warts are characterized by warts on a small base with longer, fingerlike projections and are associated with HPV 4.

Question 19

What are butcher’s warts and who is primarily affected?

Answer 19

Butcher’s warts are warts that occur in meat workers who have direct contact with wet meat, associated with HPV 7.

Question 20

What is Epidermodysplasia Verruciformis and what mutations are associated with it?

Answer 20

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.

Question 21

What are the characteristics of palmar and plantar warts?

Answer 21

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.

Question 22

What type of cancer is associated with HPV 6 and 11?

Answer 22

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.

Question 23

What are the common HPV types associated with EV presenting as widespread flaky, scaly, or flat warty lesions?

Answer 23

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.

Question 24

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?

Answer 24

The warts are likely caused by HPV 3 or 10 (plane warts). The recommended treatment is the immune modulator Imiquimod.

Question 25

A meat worker develops warts on their hands after prolonged contact with wet meat. What is the specific HPV type associated with this condition?

Answer 25

The condition is known as Butcher’s warts, and it is associated with HPV 7.

Question 26

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?

Answer 26

The likely diagnosis is Epidermodysplasia Verruciformis-like syndrome. HPV types 9, 12, 15, 19, 22-25, 36-38, and 80 are implicated.

Question 27

A patient presents with longstanding, slowly enlarging warty areas on the soles. What is the likely diagnosis, and which HPV types are associated?

Answer 27

The likely diagnosis is Carcinoma cuniculatum or verrucous carcinoma, associated with HPV 6 and 11.

Question 28

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?

Answer 28

The condition is called palmar and plantar warts (Myrrmecia), and it is most likely caused by HPV 1.

Question 29

A patient with a history of chronic sun exposure develops skin SCC. What HPV types are commonly associated with this condition?

Answer 29

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.

Question 30

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?

Answer 30

The condition is called mosaic warts, and it is caused by HPV 48.

Question 31

A patient presents with benign scaly lesions on the face and hands. What is the likely diagnosis, and which HPV types are implicated?

Answer 31

The likely diagnosis is Epidermodysplasia Verruciformis-like syndrome, with HPV types 9, 12, 15, 19, 22-25, 36-38, and 80 implicated.

Question 32

A patient presents with warts on a small base with fingerlike projections. What is the condition called, and which HPV type is responsible?

Answer 32

The condition is called filiform warts, and it is caused by HPV 4.

Question 33

A patient presents with warts on the hands and feet. What are the most common HPV types responsible for common warts?

Answer 33

The most common HPV types responsible for common warts are HPV 2, 27, and 57.

Question 34

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?

Answer 34

The likely diagnosis is Epidermodysplasia Verruciformis. The genetic mutation associated is in the EVER1 and EVER2 genes.

Question 35

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?

Answer 35

The condition is called palmar and plantar warts (Myrrmecia), and it is caused by HPV 1.

Question 36

A patient presents with warts on the face and hands. What is the likely diagnosis, and which HPV types are implicated?

Answer 36

The likely diagnosis is Epidermodysplasia Verruciformis-like syndrome, with HPV types 9, 12, 15, 19, 22-25, 36-38, and 80 implicated.

Question 37

What are the common clinical features of anogenital warts caused by HPV 6 and 11?

Answer 37

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.

Question 38

What is the first-line treatment for anogenital warts caused by HPV 6 and 11?

Answer 38

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.

Question 39

What are the potential complications of oral warts caused by HPV 6 and 11?

Answer 39

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.

Question 40

What is the significance of the quadrivalent anti-HPV vaccine in relation to genital warts?

Answer 40

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.

Question 41

What are the histological features associated with anogenital intraepithelial neoplasia and cancer caused by HPV 16?

Answer 41

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.

Question 42

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?

Answer 42

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.

Question 43

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?

Answer 43

The differential diagnosis includes Bowenoid papulosis and seborrheic keratosis. A biopsy is recommended for diagnosis.

Question 44

A patient with HIV develops cauliflower-shaped warts in the oral cavity. What is the likely diagnosis, and which HPV types are responsible?

Answer 44

The likely diagnosis is oral warts, and the responsible HPV types are HPV 6 and 11.

Question 45

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?

Answer 45

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.

Question 46

A patient presents with warts on the lips and oral cavity. What is the likely diagnosis, and how is it transmitted?

Answer 46

The likely diagnosis is oral warts caused by HPV 6 and 11. It is transmitted sexually and is regarded as an STD.

Question 47

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?

Answer 47

The likely diagnosis is anogenital warts caused by HPV 6 or 11. The first-line treatment is topical Podophyllotoxin or Imiquimod.

Question 48

A patient presents with a history of HPV infection and develops metastatic skin SCC. What preventive measures could have reduced the risk?

Answer 48

Preventive measures include sun protection, regular surveillance for SCC, and early treatment of suspicious lesions.

Question 49

What is the likely diagnosis for warts on the upper respiratory tract, and what is a common complication in childhood?

Answer 49

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.

Question 50

What is the lifetime risk of developing cancer for an individual with Atypical Glandular Neoplasia (AGIN)?

Answer 50

An individual with AGIN has a 5% lifetime risk of developing cancer.

Question 51

What are the clinical features associated with HPV-related Oral and Oropharyngeal Squamous Cell Carcinoma (HPV 16)?

Answer 51

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.

Question 52

What are the main histological findings in HPV infections?

Answer 52

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.

Question 53

What are the general treatment strategies for warts caused by HPV?

Answer 53

Treatment strategies aim to: 1. Damage the infected epithelium and debulk the lesions (especially for immunocompromised patients). 2. Have some effect on the virus life cycle (e.g., using Podophyllotoxin or retinoids). 3. Stimulate an immune response.

Question 54

What are the most commonly used destructive treatments for warts?

Answer 54

The most commonly used destructive treatments for warts include: 1. Silver nitrate 2. Phenol 3. Mono- or trichloroacetic acid 4. Laser or excisional surgery.

Question 55

What is the most likely HPV type involved in squamous cell carcinoma in the oropharynx, and what preventive measure could reduce the incidence?

Answer 55

The most likely HPV type involved is HPV 16. The anti-HPV vaccine may reduce the incidence of malignancy.

Question 56

What is the condition called when a patient with immunosuppression develops large areas of warts on the skin and mucous membranes?

Answer 56

The condition is called generalized verrucosis.

Question 57

What HPV type is most likely involved in a silent infection in the oropharynx, and what are the traditional risk factors?

Answer 57

The most likely HPV type involved is HPV 16. Traditional risk factors include smoking and alcohol, but HPV infection is now a stronger association.

Question 58

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?

Answer 58

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.

Question 59

What is the recommended preventive measure for a patient with a history of HPV infection who develops oropharyngeal SCC?

Answer 59

The most likely HPV type involved is HPV 16. The recommended preventive measure is the anti-HPV vaccine.

Question 60

What is the recommended duration for regular treatment of warts?

Answer 60

Regular treatment for at least 3 months or longer is likely to be required.

Question 61

What is the clearance rate for most common treatments compared to placebo?

Answer 61

The clearance rate for most common treatments is 60-70%, compared with 30% clearing up the placebo.

Question 62

What is the most common modality of treatment for warts? Give some examples.

Answer 62

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)

Question 63

HPV strains involves in epidermoid plantar cysts?

Answer 63

HPV 57 and 60.

Question 64

T or F: The anti-HPV vaccine may reduce incidence of malignancy in male patients with silent oropharyngeal HPV 16 infection.

Answer 64

True.