Detection of Felis catus papillomavirus type 2 within multicentric basosquamous carcinoma in a domestic cat.

A 12-year-old neutered male domestic shorthair cat was presented with a 3-year history of multiple nonpruritic, ulcerated, plaque-like skin lesions but no other clinical signs. A systemic examination revealed mild lymphadenopathy. Histopathologic analysis of the skin lesions revealed multicentric basosquamous carcinoma (BSC). Immunohistochemical analysis, PCR, and sequencing detected Felis catus papillomavirus type 2 (FcaPV-2) within the tumors. As BSC is rare in cats, clinical behavior has not been established. To our knowledge, this is the first case report to demonstrate detection of FcaPV-2 within a BSC in a domestic cat.

The role of human papillomavirus infection in the pathogenesis of penile squamous cell carcinomas.

Emerging evidence suggests that penile cancer follows 2 etiologic pathways, 1 related to human papillomavirus (HPV) infection and the other related to other factors including phimosis, chronic inflammation, and lichen sclerosus. HPV DNA is found in 47% to 48% of all penile tumors, and most of these cases correspond to high-risk genotypes, preferentially HPV-16. HPV status is associated with histologic subtype, with higher detection ratios in warty-basaloid carcinomas and lower detection ratios in keratinizing variants (ie, verrucous, papillary, and usual squamous cell carcinomas). It is the cell type, rather than a distinctive architecture, that is more strongly associated with HPV presence. The detection ratio is higher in tumors composed entirely or partially of cells with basaloid features. In addition, a few studies have evaluated the impact of HPV infection on the prognosis of patients with penile cancer. However, results are controversial, and more data are needed to clarify this matter. A proper understanding of the role of HPV in penile carcinogenesis might help in planning intervention strategies such as vaccination against HPV infection.

Histologic classification of penile intraepithelial neoplasia.

Penile squamous cell carcinomas (SCCs) and their corresponding precancerous lesions can be classified in 2 major groups: human papillomavirus (HPV) related and HPV unrelated. In the former (warty and basaloid SCC), there is a predominance of undifferentiated basaloid cells. In the latter (eg, usual, papillary, and verrucous SCC), the predominant cell is larger with abundant eosinophilic cytoplasm. Based on these morphologic features, a new term, "penile intraepithelial neoplasia" (PeIN), was proposed. PeIN was further subclassified into differentiated and undifferentiated, with the latter being subdivided into basaloid, warty, and warty-basaloid subtypes. Macroscopically, PeIN subtypes are indistinguishable. Microscopically, differentiated PeIN is characterized by acanthosis, parakeratosis, enlarged keratinocytes with abundant "pink" cytoplasm (abnormal maturation), and hyperchromatic cells in the basal layer. In basaloid PeIN the epithelium is replaced by a monotonous population of uniform, small, round, and basophilic cells. Warty PeIN is characterized by a spiky surface, prominent atypical parakeratosis, and pleomorphic koilocytosis. Warty-basaloid PeIN show features of both warty and basaloid PeIN. There is a significant association of subtypes of PeIN with specific variants of invasive SCCs. This is a simple and reproducible nomenclature for penile precancerous lesions based on cell type and differentiation. It takes into account the similarities between vulvar and penile pathology and the hypothesis of a bimodal pathway of penile cancer progression.

Basaloid squamous cell carcinoma of the esophagus: assessment for high-risk human papillomavirus and related molecular markers.

Basaloid squamous cell carcinoma (BSCC) of the esophagus is rare, historically confused for adenoid cystic carcinoma, and recently shown to behave similar to conventional, keratinizing esophageal squamous cell carcinoma. At other sites (eg, oropharynx, anogenital tract) the basaloid phenotype is frequently associated with the presence of high-risk human papillomavirus (HPV). HPVs role in esophageal squamous cell carcinomas is less certain, and to our knowledge, a direct examination of esophageal BSCC for high-risk HPV has not been performed earlier. Nine cases of esophageal BSCC were retrieved from our surgical pathology files. Twenty-two cases of keratinizing esophageal squamous cell carcinoma served as controls. In situ hybridization (ISH) for high-risk HPV and immunohistochemistry for related molecular markers including p53, cyclin D1, and p16 (scored 0 to 4+ based on percentage of cells staining; p53 additionally scored for intensity) were performed. HPV ISH was nonreactive in all tested cases. Compared with controls, BSCC showed less immunoreactivity for p16 and p53 (P=0.003, 0.009). Esophageal BSCC is negative for high-risk HPV by ISH, distinguishing these lesions from other BSCCs. Differential p16 and p53 expression in BSCC suggests that these tumors are molecularly distinct from conventional esophageal squamous cell carcinomas.

Bidirectional association of anogenital and oral cavity/pharyngeal carcinomas in men.

OBJECTIVE: To test the hypothesis of a bidirectional association of anogenital and oral cavity/pharyngeal human papillomavirus (HPV)-associated cancers in men. DESIGN: Population-based epidemiological study using the Surveillance, Epidemiology, and End Results cancer database. SETTING: Population-based cancer study involving patients receiving care in the United States. PARTICIPANTS: The study included 47,308 men 20 years and older with an index oral cavity/pharyngeal or anogenital cancer. MAIN OUTCOME MEASURE: Second primary HPV-associated cancers (anogenital or oral cavity/pharyngeal) or HPV-unrelated cancers (prostate, bladder, or colon). RESULTS: The standardized incidence ratio (SIR) was elevated for both anogenital cancer following oral cavity/pharyngeal cancer (SIR, 1.9; 95% confidence interval [CI], 1.2-2.7) and oral cavity/pharyngeal cancer following anogenital cancer (SIR, 3.0; 95% CI, 2.1-4.2). The increase in SIR was most pronounced for tonsillar cancer following anal cancer (SIR, 8.4; 95% CI, 2.7-19.6). The risk of second primary HPV-associated cancers did not vary significantly by age, race, year of diagnosis, or geographic location but was greater among never-married men, particularly for anal cancer following oral cavity/pharyngeal cancer (SIR, 6.5; 95% CI,1.8-16.7 in never-married men, but SIR, 1.6; 95% CI, 0.7-3.1 in ever-married men) and for tonsillar cancer following anogenital cancer (SIR, 13.0; 95% CI, 3.5-33.2 in never-married men, but SIR, 3.8; 95% CI, 1.0-9.7 in ever-married men). Other than a slightly increased risk of tongue cancer following colon cancer (SIR, 1.3; 95% CI, 1.1-1.6), there was no increased risk of oral cavity/pharyngeal or anogenital cancer following HPV-unrelated cancers or vice versa. CONCLUSION: The association between index and second primary anogenital and oral cavity/pharyngeal cancers, strongest in never-married men, supports the influence of sexual behavior on the risk of HPV-associated head and neck cancers.

Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status.

Basaloid squamous cell carcinoma (BSCC) of the head and neck is set apart as a distinct subtype of squamous cell carcinoma on the basis of its basaloid appearance and aggressive behavior. The purpose of this study was to determine whether BSCC could be further subdivided on the basis of human papillomavirus 16 (HPV16) status. HPV16 in situ hybridization was performed on 53 BSCCs of the head and neck. Of the 53 BSCCs, 21 (40%) arose in the oropharynx and 32 (60%) arose in nonoropharyngeal sites. HPV16 was detected in 34% of BSCCs overall, but the frequency varied by site. HPV16 was detected in 16 of 21 (76%) BSCCs of the oropharynx, but in only 2 of 32 (6%) BSCCs from nonoropharyngeal sites (P<0.0001, Fisher exact). The absence of HPV16 was significantly associated with decreased overall survival (Hazard ratio=17.1; 95% confidence interval=7.2-40.3, log-rank P=0.0001), even though patients with HPV16-positive carcinomas were more likely to present with lymph nodes metastases (P=0.01, Fisher exact). Morphologic similarities aside, BSCCs are composed of a mixed group of tumors that can be separated on the basis of HPV16 status. The distinction is important. HPV16-positivity in squamous cell carcinomas of the head and neck is now recognized as a powerful indicator of improved patient survival. HPV16 detection thus permits resolution of a less aggressive component within a high-grade subtype of head and neck carcinoma.

Genetic characterization of the first chiropteran papillomavirus, isolated from a basosquamous carcinoma in an Egyptian fruit bat: the Rousettus aegyptiacus papillomavirus type 1.

The complete genomic DNA of a novel papillomavirus (PV) was isolated from a basosquamous carcinoma on the wing of an Egyptian fruit bat (Rousettus aegyptiacus). Initial short sequences of the E1 and L1 genes of this virus were retrieved by PCR with degenerate papillomavirus-specific primers, and the entire R. aegyptiacus papillomavirus type 1 (RaPV-1) DNA was then amplified by long template PCR, cloned and sequenced with a transposon insertion method. The RaPV-1 genome counts 7970 basepairs and contains the typical papillomavirus open reading frames (ORF) (E1, E2, E4, E6, E7, L1 and L2). Based on a concatenated alignment of the E1, E2, L1 and L2 open reading frames of RaPV-1 and 46 other human and animal papillomavirus type species, a neighbor-joining phylogenetic tree was constructed. This phylogenetic analysis shows that RaPV-1 has a close-to-root position in the papillomavirus evolutionary tree. Since RaPV-1 is only distantly related to other papillomaviruses (with maximally 50% nucleotide sequence identity across the L1 open reading frame), it cannot be assigned to one of the existing papillomavirus genera and therefore represents the first member of a novel, as yet unnamed, close-to-root papillomavirus genus. This is the first time a papillomavirus has been isolated and characterized from a member of the Chiroptera order.

Clinicopathologic study of basaloid squamous carcinoma of the upper aerodigestive tract.

The clinicopathologic and immunohistochemical characteristics of nine cases of basaloid squamous carcinoma (BSC) of the upper aerodigestive tract are reported, along with the results of an in situ hybridization for human papilloma virus (HPV) DNA. The cases were selected through a review of 237 head and neck carcinomas, and were located in the supraglottic larynx (5), hypopharynx (2), and the base of tongue (2). The patients were 7 males and 2 females with the mean age of 62. BSCs were histologically characterized by lobules and nests of basaloid cells with scanty cytoplasm, comedonecrosis and adenoid features, and by concomitant presence of squamous cell carcinoma. Immunohistochemically, all BSCs showed positivity for high molecular weight cytokeratin (HMW CK) with heterogeneous or diffuse staining pattern, but lacked reactivity for neuroendocrine markers and bcl-2 oncoprotein. No HPV DNA was detected in BSCs. This study reaffirms that BSC is a rare carcinoma with a peculiar topographic distribution and distinct pathologic features.

Intraoral squamous cell carcinoma in human immunodeficiency virus infection. A clinicopathologic study.

The purpose of this study was to characterize the clinical and histological features of intraoral squamous cell carcinoma in men who were seropositive for the human immunodeficiency virus and to evaluate viral cofactors (human papillomavirus, herpes simplex virus, Epstein-Barr virus), proliferative index (proliferating cell nuclear antigen), a factor associated with invasion (cathepsin D), and mutated tumor suppressor gene and proto-oncogene products (mutated p53, c-erbB-2). Four men who were seropositive for the human immunodeficiency virus and had acquired immunodeficiency syndrome presented with painful oral lesions of variable duration. Oral cancer risk factors included heavy tobacco use (four of four), heavy alcohol use (three of four), and previous radiotherapy (one of four). The lesions consisted of ulcers (two of four), a fungating mass (one of four), and papillary erythroplakia (one of four). Incisional biopsy specimens were obtained. High-stringency in situ hybridization was performed with DNA probes to the human papillomavirus (types 6/11; 16/18; 31/33/35) and Epstein-Barr virus: Immunocytochemical studies for the herpes simplex virus, proliferating cell nuclear antigen, cathepsin D, mutated p53, and c-erbB-2 were performed. Two lesions were moderately differentiated squamous cell carcinoma, one lesion was a basaloid squamous cell carcinoma, and one was carcinoma in situ. Stage of disease at diagnosis was II (one of four), III (two of four), and IV (one of four). Three cases were positive for the human papillomavirus, one case was positive for Epstein-Barr virus, and three cases were positive for the herpes simplex virus. C-erbB-2 was focally positive in one case, and mutated p53 was positive in a separate case.(ABSTRACT TRUNCATED AT 250 WORDS)