![]() E4 protein is an immunohistochemical biomarker of productive HPV infection and associated with a low short-term progression risk ( Am J Surg Pathol 2015 39:1518).Cytoplasm staining of the tumor cells with E6 (Abcam, Clone C1P5) or E7 (Chemicon, Clone TGV701Y) oncoproteins is considered positive ( Anticancer Res 2016 36:319).Nuclear and cytoplasmic expression of p16 in ≥ 70% of tumor cells is required for the diagnosis of HPV positive oropharyngeal squamous cell carcinoma ( Arch Pathol Lab Med 2018 142:559).Patchy / weak or cytoplasmatic only staining should be considered negative.Diffuse and strong nuclear or nuclear and cytoplasmatic staining involving the basal and parabasal layers is considered positive (block-like staining).Dot-like signals of varying sizes in the cytoplasm and nuclei of tumor cells ( Hum Pathol 2017 63:184).Punctate and dot-like signals within tumor nuclei indicate the presence of integrated HPV, while diffuse nuclear staining is thought to indicate the presence of episomal HPV genomes ( Korean J Pathol 2010 44:513).Table: HPV classification according to International Agency for Research on Cancer Monograph Working Group ( Lancet Oncol 2009 10:321) Limited evidence for skin cancer in patients with epidermodysplasia verruciformis Limited evidence in humans for cervical cancerĬlassified by phylogenetic analogy to HPV types with sufficient or limited evidence in humans Limited evidence in humans and strong mechanistic evidence for cervical cancer High risk HPV is likely to be a causative agent of some low grade bladder carcinomas ( Cancer 2011 117:2067).Certain subtypes of HPVs are the causative agents of cervical (99%), penile, vulvar and anal carcinomas and oropharyngeal carcinomas ( Nat Rev Cancer 2010 10:550, Vaccine 2006 24:S3/11).Only a fraction of women infected with high risk HPVs develop cervical cancer, indicating that additional factors must contribute to malignant progression ( Nat Rev Cancer 2010 10:550).High risk HPVs are associated with intraepithelial neoplasia and cancers ( Virus Res 2009 143:195).Low risk HPVs are associated with benign warts ( Virus Res 2009 143:195). ![]() HPVs are clinically classified as low risk and high risk, based on the propensity of the HPV associated lesions to undergo malignant progression ( Virus Res 2009 143:195).More than 100 HPV types have been differentiated molecularly and at least 40 of them have a tropism for anogenital mucosa ( Sci Rep 2018 8:11313). ![]()
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