• Human papilloma viruses (HPV) comprise a large group of at least 200 genotypes of DNA viruses that infect the skin and mucosa.

• Different genotypes cause different skin lesions (Table 66.1).

– Clinical variants differ as to anatomic location, morphology, histopathology, and HPV subtype; correlation of clinical and histopathologic findings is particularly important for bowenoid papulosis and verrucous carcinoma in order to prevent over- or undertreatment, respectively.

• Nongenital warts.

– Transmitted via person-to-person contact or contact with contaminated surfaces/objects.

– Prevalence of 20% in schoolchildren.

– A third or more self-regress within 1–2 years.

– Numerous warts or persistent/progressive warts should prompt consideration of immunosuppression, defects in cellular immunity, or other syndromes [e.g. HIV infection, epidermodysplasia verruciformis, WHIM syndrome (see Chapter 49)].

• Anogenital infection with HPV.

– Sexually transmitted; in young children may also be acquired perinatally or via the same routes as nongenital warts.

– May be subclinical.

• High-risk HPV types, especially 16 and 18, are a major cause of cervical cancer as well as cutaneous (periungual SCC) and other mucosal intraepithelial neoplasias or SCCs, in particular vaginal, vulvar, penile, and anal; HPV-associated oropharyngeal SCC is a recently identified specific subtype.

• Rx.

– If desired, focuses on destruction of visible lesions or induction of an immune response.

– Effective targeted antiviral treatments are not available.

• Prevention: prophylactic HPV vaccines (e.g. Cervarix^® and Gardasil^®) are available for genital warts and cervical cancer.

• Any site, but commonly on the fingers, dorsal hands, and/or sites prone to trauma (Figs. 66.1 and 66.2).

• Hyperkeratotic, exophytic or dome-shaped papules or plaques with punctate black dots (thrombosed capillaries) that may require paring to see (Fig. 66.3).

• Histopathology: papillomatosis, acanthosis, hypergranulosis; epidermal keratinocytes have haloes around their nuclei (koilocytes).

• DDx: seborrheic keratosis, actinic keratosis, cutaneous horn, SCC (especially periungual), trichilemmoma, Spitz nevus.

• Rx: outlined in Fig. 66.4; may regress spontaneously within 1–2 years; may be difficult to eradicate.

• Thick, exo- and endophytic hyperkeratotic papules and plaques (Fig. 66.5); coalescence of lesions can lead to extensive areas of involvement referred to as mosaic warts.

• May see sloping sides and a central depression (the term myrmecia is used because it can resemble an anthill); tender with pressure (Fig. 66.6).

• DDx: corns (clavi; see Chapter 74), punctate palmoplantar keratoderma (see Table 47.1), arsenical keratoses, SCC, amelanotic melanoma.

• Rx: overlaps with Rx of common warts (see Fig. 66.4).

• Commonly on the dorsal hands, arms, and face, as well as the legs (exacerbated by shaving).

• Skin-colored to pink or brown (sometimes hypopigmented in darker skin), minimally elevated papules; the surface is smooth and often flat-topped (Fig. 66.7).

• DDx: small seborrheic keratoses, common warts, Gottron’s papules of dermatomyositis, lichen nitidus, lichen planus, acrokeratosis verruciformis (see Chapter 48), epidermodysplasia verruciformis (see below).

• Rx.

– If a few lesions, destructive or ablative therapies (e.g. cryosurgery, trichloroacetic acid; see Fig. 66.4).

– If numerous, topical application of irritants (e.g. retinoids), immunotherapy (see Fig. 66.4), topical 5-fluorouracil.

• Buccal, gingival, and labial mucosae as well as tongue and hard palate (Fig. 66.8).

• Small, soft, mucosal-colored to white, slightly elevated papillomatous papules.

• DDx: Heck’s disease (focal epithelial hyperplasia; multiple white to pink sessile papules; secondary to HPV types 13 and 32), early SCC, verrucous proliferative leukoplakia, bite fibroma.

• Involve primarily the anogenital region.

• Range from discrete, sessile, smooth-surfaced papillomas to large cauliflower-like lesions (Figs. 66.9 and 66.10).

• Skin-colored to pink to brown.

• If present in children, especially those >3 years of age, the possibility of sexual abuse should be considered (see Chapter 75).

• DDx: seborrheic keratosis, skin tag, molluscum contagiosum, Bowenoid papulosis, SCC, pearly penile papules (see Chapter 95), free sebaceous glands, condyloma lata of secondary syphilis.

• Rx: outlined in Fig. 66.11.

• Similar to condylomata acuminata, primarily in the anogenital region.

• Multiple pink to red-brown smooth to warty papules or plaques (Fig. 66.12; see Fig. 60.9).

• Histopathology: numerous mitoses scattered throughout the epidermis (which distinguishes it from condyloma acuminatum); keratinocytes may show less atypia than in an SCC.

• Rx: outlined in Fig. 66.11.

• Favors the glabrous skin of the vulva or penis and the periungual region.

• Well-demarcated pink to red plaque (Fig. 66.13).

• DDx: dermatitis, psoriasis, Rx-resistant periungual wart, lichen sclerosus, erosive lichen planus, candidiasis especially in uncircumcised male, extramammary Paget’s disease, Zoon’s balantis, amelanotic melanoma.

• Rx: excision, Mohs surgery, or other destructive modalities depending on patient/lesion characteristics; imiquimod with careful re-evaluation.

• Low-grade malignancy that is locally invasive and destructive, but rarely metastasizes; lesions can attain a large size when left untreated.

• Major types.

– Buschke–Löwenstein tumor (Fig. 66.14) – anogenital region; fistulas and/or abscesses may be present.

– Oral florid papillomatosis – oral mucosa or perinasal sinuses – pebbly confluence of whitish papillomas.

– Epithelioma cuniculatum – plantar surface – irregularly shaped, well-demarcated, verrucous nodule, often several centimeters in diameter.

• Rx: excision.

• Cutaneous infection with particular HPV types in patients with an inherited predisposition [mutations in TMC6 (EVER1), TMC8 (EVER2)] or acquired immunosuppression (e.g. HIV infection); see Table 66.1.

• Widespread lesions that begin to appear during childhood (inherited form), with a predisposition for sun-exposed areas.

• Lesions vary in color from white to pink to brown and can resemble flat warts or tinea versicolor (Fig. 66.15).

• Distinctive histopathology with expanded gray-blue cytoplasm within the keratinocytes of the upper stratum spinosum.

• Increased risk of SCC, especially in sun-exposed areas.

• Rx: difficult (similar to that for flat warts), sun protective measures, address immunosuppression in acquired cases.

• Human papilloma viruses (HPV) comprise a large group of at least 200 genotypes of DNA viruses that infect the skin and mucosa.

• Different genotypes cause different skin lesions (Table 66.1).

– Clinical variants differ as to anatomic location, morphology, histopathology, and HPV subtype; correlation of clinical and histopathologic findings is particularly important for bowenoid papulosis and verrucous carcinoma in order to prevent over- or undertreatment, respectively.

• Nongenital warts.

– Transmitted via person-to-person contact or contact with contaminated surfaces/objects.

– Prevalence of 20% in schoolchildren.

– A third or more self-regress within 1–2 years.

– Numerous warts or persistent/progressive warts should prompt consideration of immunosuppression, defects in cellular immunity, or other syndromes [e.g. HIV infection, epidermodysplasia verruciformis, WHIM syndrome (see Chapter 49)].

• Anogenital infection with HPV.

– Sexually transmitted; in young children may also be acquired perinatally or via the same routes as nongenital warts.

– May be subclinical.

• High-risk HPV types, especially 16 and 18, are a major cause of cervical cancer as well as cutaneous (periungual SCC) and other mucosal intraepithelial neoplasias or SCCs, in particular vaginal, vulvar, penile, and anal; HPV-associated oropharyngeal SCC is a recently identified specific subtype.

• Rx.

– If desired, focuses on destruction of visible lesions or induction of an immune response.

– Effective targeted antiviral treatments are not available.

• Prevention: prophylactic HPV vaccines (e.g. Cervarix^® and Gardasil^®) are available for genital warts and cervical cancer.

• Any site, but commonly on the fingers, dorsal hands, and/or sites prone to trauma (Figs. 66.1 and 66.2).

• Hyperkeratotic, exophytic or dome-shaped papules or plaques with punctate black dots (thrombosed capillaries) that may require paring to see (Fig. 66.3).

• Histopathology: papillomatosis, acanthosis, hypergranulosis; epidermal keratinocytes have haloes around their nuclei (koilocytes).

• DDx: seborrheic keratosis, actinic keratosis, cutaneous horn, SCC (especially periungual), trichilemmoma, Spitz nevus.

• Rx: outlined in Fig. 66.4; may regress spontaneously within 1–2 years; may be difficult to eradicate.