Chapter 102 : Human Papillomaviruses

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The majority of identified human papillomaviruses (HPVs) with clinical significance are found in the genus , which includes types infecting the genital and nongenital mucosal and genital cutaneous surfaces as well as the genotypes associated with human cancers. The natural history of oral HPV less is only beginning to be evaluated, though it is clear that while high-risk (HR) HPV infection is associated with a subset of head and neck squamous cell cancers, the prevalence of oral HPV infection in the general population is substantially lower than the HPV prevalence in the genital tracts of men and women. Sample collection, transport, and storage recommendations of specimens vary based on the purpose and method of HPV testing. The morphological cellular changes characteristic of HPV infection and associated neoplasia are the basis for standard cervical cytology and are classified based on the Bethesda system. HPV DNA tests are typically performed on one to three 10-µm sections of formalin-fixed paraffin-embedded (FFPE) tissue. Sections are deparaffinized with octane and digested with a buffer containing proteinase K and a nonionic detergent. The number of commercially available assays for HPV detection has increased dramatically in recent years. HPV RNA:DNA hybrids are detected using a sandwich enzyme-linked immunosorbent assay-type reaction. One of the most characteristic features of HPV infection is the multiplicity of genotypes known to infect the anogenital tract and oral cavity. Complete genotyping has been incredibly useful as a research tool to evaluate the natural history of all genotypes in epidemiological studies.

Citation: Gravitt P, Ginocchio C. 2011. Human Papillomaviruses, p 1612-1623. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch102

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Enzyme-Linked Immunosorbent Assay
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Image of FIGURE 1

Photograph of KA. LSILs on Pap smears are characterized by high nuclear/cytoplasmic ratios and the presence of KA, which is defined as the presence of nuclear atypia as well as a clearly defined perinuclear halo in cervical epithelial cells. Photograph courtesy of Patricia Wasserman, Division of Cytopathology, Department of Pathology and Laboratory Medicine, North Shore-LIJ Health System, Lake Success, NY.

Citation: Gravitt P, Ginocchio C. 2011. Human Papillomaviruses, p 1612-1623. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch102
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Image of FIGURE 2

Graphic representation of the Invader chemistry in the Cervista HR HPV test. Courtesy of Hologic, Inc., and affiliates.

Citation: Gravitt P, Ginocchio C. 2011. Human Papillomaviruses, p 1612-1623. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch102
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Image of FIGURE 3

American Society for Colposcopy and Cervical Pathology 2006 consensus conference recommendations for HPV type 16 or 18 detection (from http://www.asccp.org/pdfs/consensus/clinical_update_20090408.pdf).

Citation: Gravitt P, Ginocchio C. 2011. Human Papillomaviruses, p 1612-1623. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch102
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Human alphapapillomavirus genotype diversity and clinical manifestations

HPVs were recently reclassified by the International Committee on Taxonomy of Viruses (ICTV). The new classification (species, ICTV) and the historical classification (species, common use) are both represented. MMPV, PV. Species are listed by type; e.g., HPV32 is HPV type 32.

Citation: Gravitt P, Ginocchio C. 2011. Human Papillomaviruses, p 1612-1623. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch102
Generic image for table

Clinical indications for appropriate use of HPV tests

Adapted from reference . ASC-US: atypical squamous cells of undetermined significance; AGC, atypical glandular cells; ASC-H, atypical squamous cells, cannot exclude a high-grade SIL.

Citation: Gravitt P, Ginocchio C. 2011. Human Papillomaviruses, p 1612-1623. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch102
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Commercially available HPV assays

NASBA, nucleic acid sequence-based amplification; TMA, transcription-mediated amplification; ASC-US, atypical squamous cells of undetermined significance.

Citation: Gravitt P, Ginocchio C. 2011. Human Papillomaviruses, p 1612-1623. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch102

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