Human Papillomavirus (HPV)

  • Figure 4.5 A: Pityriasis rosea, face (Courtesy of Dr. Paul Getz) B: Kaposi’s sarcoma (Courtesy of National Cancer Institute) C: Verruca vulgaris
    Figure 4.5
    A: Pityriasis rosea, face (Courtesy of
    Dr. Paul Getz
    ) B: Kaposi’s sarcoma
    Courtesy of National Cancer Institute
    C: Verruca vulgaris
    Figure 4.6 A: Bowenoid papulosis* B: Verrucous carcinoma on lip in betel leaf chewer* *Courtesy of Dr. Shyam B. Verma, Vadodara, India
    Figure 4.6
    A: Bowenoid papulosis*
    B: Verrucous carcinoma on lip
    in betel leaf chewer*
    *Courtesy of Dr. Shyam B.
    Verma, Vadodara, India
    Non-enveloped dsDNA virus with more than 100 different HPV types; infects epithelia and mucosa
  • Genome encodes “E” (early) and “L” (late) proteins
    • “E” proteins (E1–E7) code for viral DNA replication; E6 and E7 oncogenes lead to keratinocyte immortalization; low levels expressed in basal layer
    • “L” proteins (L1 and L2) code for viral structural proteins (form outer shell: virion), expressed in superficial epithelium
  • Transmission mainly via direct skin contact, less likely via fomites; basal keratinocyte target of HPV (long-term reservoir of viral DNA)
  • Divided into nongenital and genital infections; also divided into benign or low risk (HPV 6/11) and high risk (HPV 16/18) types
  • Gardasil® vaccine: composed of L1 capsid protein with four types of recombinant HPV (type 6, 11, 16, 18)
  • Cervarix® vaccine: L1 protein for HPV 16 and 18
  • Clinical manifestations of HPV infection:
    • Common, plantar, and flat warts (Figure 4.5C)
    • Condyloma acuminata: lesions without significant scale in genital area
    • Bowenoid papulosis: red-brown papules or plaques involving genital and/or perineal area (clinically appear as genital warts, but histology consistent with Bowen’s disease) (Figure 4.6A)
    • Verrucous carcinoma: “semi-malignant” (Figure 4.6B)
      • Florid oral papillomatosis: widespread verrucous carcinoma in oral cavity
      • Buschke–Lowenstein tumor: large cauliflower-like tumor of anorectum and external genital, focal malignant transformation may occur
      • Epithelioma cuniculatum of sole: slow-growing warty mass on sole
    • Focal epithelial hyperplasia (Heck’s disease): papules on buccal, gingival, labial mucosa resembling flat warts
    • Epidermodysplasia verruciformis: sporadic or AR inheritance, abnormal susceptibility of skin to HPV; red-brown macules with mild scale on face/trunk or flat-topped papules on hands resembling flat warts (malignant transformation in 50% patients)
  • Histology: papillomatosis, massive orthokeratosis, columns of parakeratosis, coarse keratohyalin granules of variable size, vacuolated cells (koilocytes), dilated and thrombosed capillaries
   
 
Table 4-1 HPV Subtypes
 LesionHPV Types
(Frequent)
HPV Types
(Less Frequent)
 
Common wart
1, 2, 4
26, 27, 29, 41, 57, 60, 63, 65
 
Plantar wart
1
2, 4, 63
 
Flat wart
3, 10
28, 29
 
Butcher’s wart
2, 7
1, 2, 3, 4, 10, 28
 
Epidermodysplasia
verruciformis (EV)
2, 3, 5, 8–10, 12, 14, 15, 17
19–25, 36–38, 46, 47, 49, 50
 
Focal epithelial
hyperplasia (Heck’s)
13, 32
 
{Different sources will have conflicting
HPV types for same entity}
 
Verrucous carcinoma
6, 11
 
 
Condyloma acuminata
6, 11
40, 42–44, 51, 54, 55, 61, 70, 72, 81
 
Bowenoid papulosis
16, 18
26, 31, 33, 35, 39, 45, 51–53, 56, 58, 59, 62, 66, 68, 73
 
Digital SCC
16
34, 35
 
SCC (in EV)
5, 8
14, 17, 20, 47
 
Cervical cancer
16, 18
31, 33, 35, 39, 45, 51, 52, 56, 58, 66, 68, 70