HPV-associated oral warts.

Human papillomavirus (HPV) is strictly epitheliotropic, infecting stratified squamous cutaneous and mucosal epithelial cells. Oral HPV infection may be subclinical or putatively associated with benign or malignant oral neoplasms. The benign HPV-associated oral lesions, focal epithelial hyperplasia (Heck disease), oral squamous cell papilloma, oral verruca vulgaris (common wart) and oral condyloma acuminatum, are collectively referred to as oral warts. Oral warts are usually asymptomatic, may be persistent or uncommonly, may regress spontaneously. HPV-associated oral warts have a prevalence of 0.5% in the general population, occur in up to 5% of HIV-seropositive subjects, and in up to 23% of HIV-seropositive subjects on highly active antiretroviral therapy. This paper is a clinico-pathological review of HPV-associated oral warts.

Oral verrucous hyperplasia: histologic classification, prognosis, and clinical implications.

BACKGROUND: Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an oral cancer. METHODS: Sixty consecutive OVH cases were collected from 2003 to 2004. Clinicopathological features and the 5-year malignant transformation rate of these 60 OVH lesions were evaluated and analyzed. RESULTS: We found that 84% of OVH lesions occurred in patients between 40 and 69 years of age. The most common site for OVH lesions was the buccal mucosa (48%), followed by the tongue (20%), palate (18%), gingiva (7%), and labial mucosa (7%). Approximately 91% of OVH patients were areca quid chewers and 89% were smokers. When 60 OVH lesions were classified into 30 plaque-typed and 30 mass-typed OVH lesions, the mass-typed OVH lesions had a higher malignant transformation rate of 17% (5/30) than the plaque-typed OVH lesions (3%, 1/30) during a mean follow-up period of 59 +/- 7 months. The mean time for malignant transformation was 22 +/- 11 months. Of the 6 OVH lesions with malignant transformation, 2 underwent total surgical excision and 4 did not receive any form of therapy. CONCLUSIONS: We conclude that OVH lesions occur more commonly on the buccal mucosa and are highly associated with the areca quid chewing and cigarette smoking habits. The overall 5-year malignant transformation rate of 60 OVH lesions was 10%. The mass-typed OVH lesions had a higher malignant transformation rate than the plaque-typed OVH lesions and thus should receive an immediate treatment, such as total surgical excision or photodynamic therapy, after the histopathologic diagnosis.

Human papilloma virus type 69 identified in a clinically aggressive plantar verruca from an HIV-positive patient.

BACKGROUND: Verrucae are caused by infection of epidermal keratinocytes by human papilloma virus (HPV). Although there are currently more than 100 known types of HPV, certain lesions are consistently caused by infection with one or a few types. Recent studies have identified the presence of unusual HPV types in anogenital and cervical condylomata (warts) of patients infected with human immunodeficiency virus (HIV). Although cutaneous verrucae are typically caused by HPV-1, HPV-2, and HPV-4, infection with HIV may predispose an individual to infection with an unusual HPV type. METHODS: We report the detection of a rare HPV type in a clinically aggressive plantar verruca from an HIV-positive patient. The viral DNA from this specimen was analyzed to identify the predominant HPV type. To complete this analysis, HPV DNA was extracted from the formalin-fixed specimen, followed by polymerase chain reaction with consensus HPV primers and digestion with a specific group of restriction endonucleases. The fragments were separated on an agarose gel, and the restriction fragment length polymorphism pattern was compared with known patterns for identification of the specific HPV type. RESULTS: Identification of HPV-69, an HPV type previously reported to be rare and associated with dysplastic lesions, was confirmed by HPV DNA dot-blot hybridization with specific DNA probes for each known HPV type. CONCLUSIONS: Plantar verrucae in HIV-positive patients may be associated with unusual HPV types and should be analyzed and treated aggressively given the potential for a more distinct clinical manifestation. Additional lesional analysis studies are needed.

Epidermodysplasia verruciformis and generalized verrucosis: the same disease?

We report a patient with epidermodysplasia verruciformis (EV) who had severe generalized verrucous skin lesions for 50 years without any immunological abnormality. Microscopic examination showed two histopathological features, including seborrhoeic keratosis and common warts. The detected human papilloma virus (HPV) types were found to be HPV 3, 50, 5, and 76, using a degenerate PCR method. EV and generalized verrucosis are distinguished by slight differences in clinical symptoms or HPV types, so there should be no apparent differential points common to both diseases. Therefore, we propose that an abnormal susceptibility specific to HPV, which is the most characteristic feature in EV, should be regarded as a differential point in these two diseases.

Human papillomavirus infections in children.

PURPOSE OF REVIEW: The human papillomavirus is a ubiquitous 55-nm DNA virus that causes a variety of clinical disease states in children, commonly referred to as warts. The natural history of warts is spontaneous regression through the development of a complex blend of cell-mediated and humoral immunity. Although spontaneous immunity can develop, as many as one third of children will have persistent human papillomavirus infection beyond 2 years. Therapeutic modalities are manifold, primarily because no therapy is universally effective. The purpose of this review is to update the reader with the latest information on the human papillomavirus and its therapeutics in children. RECENT FINDINGS: Recently, encouraging research has been conducted in human papillomavirus, including destructive and immunologic therapies. Vaccines tailored to genital human papillomavirus strains are just coming into clinical use. SUMMARY: Manipulation of the immune system through medications or vaccination will likely help contain human papillomavirus in the future and prevent secondary human papillomavirus oncogenesis of the skin and cervix.

Aggressive, multifocal oral verrucous leukoplakia: proliferative verrucous leukoplakia or not?

BACKGROUND: Some oral verrucal lesions may constitute parts of the clinicopathological spectrum of proliferative verrucous leukoplakia (PVL). Because of its idiopathic yet sinister nature, it is possible that PVL may exist in other populations. The aim of this study was to review the clinicopathological features of persistent, multifocal, oral verrucal lesions in Malaysian population. METHODS: Patients with multifocal oral verrucal lesions were selected from surgical and histopathological records. RESULTS: Nine patients of diverse ethnicity with 43 biopsies were reviewed. The mean age at the presentation was 62 years. The most frequent sites affected were gum, sulci, cheek and tongue. Indulgence in risk habits was reported in about 70% of patients. Four cases developed multifocal carcinoma from multifocal leukoplakia. CONCLUSIONS: In retrospect, none of the cases fulfilled the original PVL criteria, although three cases were suggestive of PVL. Nevertheless, these findings do not necessarily preclude the existence of PVL as a clinicopathological entity in Malaysian population.

Nongenital human papillomavirus infections.

Although genital HPV types produce a broad spectrum of disease, the nongenital types are a bit more predictive. Particularly in the immunocompromised patient, it appears as though when they become symptomatic they cause warts. These warts can be a particular problem with immunocompromised patients where the malignant potential can also be expressed. Additional understanding of the relationship between the papilloma viruses and cutaneous oncology is very important. There needs to be an application of seroepidemiologic techniques to understand better the epidemiology and further research on more effective and less painful therapies.

New types of human papillomaviruses and intracytoplasmic inclusion bodies: a classification of inclusion warts according to clinical features, histology and associated HPV types.

Two new types of intracytoplasmic inclusion bodies (ICBs) associated with distinct clinical features, and the presence of DNA of distinct types of human papillomaviruses (HPVs) are reported. One hundred and seven cutaneous warts containing ICBs were grouped into three categories according to distinct clinicopathological features: 67 were wart lesions with well-known granular (Gr)-ICB, 13 were punctate keratotic lesions with filamentous (Fl)-ICB and 31 were pigmented warts with homogeneous (Hg)-ICB. Molecular biological studies were performed in order to assess a specific association of each group of warts with distinct types of HPV. HPV-1 DNA sequences were detected in all the lesions with a Gr-ICB. Punctate keratotic lesions with Fl-ICB were associated with HPV-63, which was newly cloned from such a lesion. One of the samples also contained HPV-1 DNA. Pigmented warts with Hg-ICBs contained one of the related HPVs, i.e. HPV-4, HPV-60 or a novel type of HPV, HPV-65. Based on these associations, a classification of inclusion warts is proposed.

Nongenital warts: classification and treatment options.

Common, plantar and flat warts are the primary classes of nongenital warts. Although spontaneous remission does occur, all warts should be treated to avoid spreading. Common warts often develop in the periungual region of the fingers. This type of wart generally can be removed with cryotherapy, topical application of salicylic acid or occlusive taping. Plantar warts are found over pressure points of the heel or metatarsal heads. They are also treated with cryotherapy or salicylic acid. Flat warts are commonly seen on the dorsum of the hands or on the face. These warts are best treated with topical retinoids. Immunotherapies are being developed.

Carbon dioxide laser management of plantar verruca: a 6-year follow-up survey.

Patients receiving treatment for plantar verruca by carbon dioxide laser vaporization from 1984 through 1989 were surveyed with follow-up from 3 months to 6 years. Materials and methods, operative technique, and results were reviewed. This procedure was used as both a primary treatment as well as secondary or tertiary treatments on recalcitrant verrucae. Solitary as well as multiple or mosaic lesions were evaluated. Patients were surveyed for elimination of all verrucae, partial or complete recurrence, postoperative complications, and satisfaction. The overall success rate, considering all eight treatment categories, was 75%. Ultimate success rates ranged from 93% for solitary lesions to 62% for multiple recalcitrant lesions. The authors' findings show clinical significance in the marked differentiation of success rates in accordance with the classification scheme. That is to say, initial treatment of a solitary lesion showed a higher success rate than initial treatment of multiple lesions, and initial treatment of virgin lesions showed a higher success rate than initial treatment of recalcitrant lesions. Based on the data accumulated, the authors propose that treatment of plantar verruca be initiated early, i.e., while the lesion is solitary and has been heretofore untreated. On the other hand, those lesions having a second or third treatment by carbon dioxide laser vaporization resulted in a higher ultimate success rate than those which had only one primary treatment. The general conclusion is that carbon dioxide laser management should be considered as a viable treatment alternative in relation to other, more traditional, techniques in the treatment of plantar verruca.

A comparative study on peripheral blood lymphocyte subpopulations in different kinds of warts.

Peripheral blood T-cell subpopulations were evaluated in 36 patients with clinically different types of warts, subdivided in 4 groups (common, genital, flat and plantar warts). A significant decrease was found in OKT3 and OKT4 subsets total count and in OKT4/OKT8 ratio in patients with common and genital warts as compared with controls. Only in common and genital warts did we also observe a significant decrease of percentage of OKT4 subset. No significant difference of considered parameters was observed in flat and plantar warts as compared to controls, apart from a significant increase in number of OKT8 subset in flat warts. We then discuss this different status of C.M.I. in patients with different clinical warts, stressing the importance of various types of HPV.

Cutaneous and mucosal warts. Clinical and histopathological criteria for classification.

The clinical and histopathological study of cutaneous and mucosal warts demonstrates divergences between clinical and histopathological diagnoses among the group of myrmecias, mosaics, acrodigitate, and common warts. There is correlations criteria (when considered separately), such as hyperkeratosis and absence of keratohyaline granules in flat warts, and in ano-genital vegetations. The existence of clinical and histological overlaps emphasizes that it is not clear whether these cases are rare clinical varieties caused by as yet unknown types of human papillomaviruses, or rather by differences in the degree of keratinization at different sites in the body.

Two anatomoclinical types of warts with plantar localization: specific cytopathogenic effects of papillomavirus. Type I (HPV-1) and type 2 (HPV-2).

In this study, the clinical and histopathological aspects of 50 plantar warts are reported in relation to the type of papillomavirus present in the lesions, as detected by immunofluorescence tests, using specific guinea pig fluorescein-labelled IgG. Warts of plantar localization are not caused by the same human papillomavirus (HPV) since they are found to be associated with both HPV type 1 (HPV-1) and HPV type 2 (HPV-2). HPV-1 is always associated with deep and painful plantar warts (myrmecia), whereas HPV-2 is found to be associated with superficial, painless plantar warts (vulgaris or often mosaic type). Histologically, these two types of plantar warts are quite different. In myrmecia (HPV-1), characterized by an endophytic growth, large eosinophilic, keratohyaline-like granules are observed in the cytoplasm and nucleus of infected, often vacuolated cells. These granules appear early in stratum spinosum and are very numerous in stratum granulosum. In the mosaic type (HPV-2), the histopathological aspect is not different from that of common warts; these lesions have an exophytic growth and are characterized by foci of clear vacuolized cells which are found in stratum granulosum. Their cytoplasm contains round, basophilic keratohyalin granules which often have a heterogenous aspect. These differences are observed in other localizations of morphologically related warts associated with HPV-1 and HPV-2 and seem to be related to a specific cytopathogenic effect of HPV-1 an HPV-2 in human papillomas.

[A contribution to the classification of seborrheic keratoses (author's transl)]. / Ein Beitrag zur Systematik der seborrhoischen Warzen

A clinico-statistical study is reported, basing on a material of 639 excised tumours which were defined histologically as seborrheic keratoses. All statements concerning clinical diagnoses and differential diagnoses, localization, development, age and sex of patients were transferred to punch cards. By means of a suitable EDA program, basic counts and a multidimensional analysis of conditioned frequencies [14] were performed. The results indicate, that the different clinical forms of seborrheic warts, often discriminated in the literature, are variants of the same entity.