Papillomaviruses Likelihood of Secondary Transmission
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APPENDIX 2 Papillomaviruses Likelihood of Secondary Transmission: • High by direct contact, especially in older children Disease Agent: and young adults • Human papillomavirus (HPV) • High by sexual contact Disease Agent Characteristics: At-Risk Populations: • Family: Papillomaviridae; Genus: Alpha-Papilloma- • Older children and young adults (nongenital skin virus warts) • Virion morphology and size: Nonenveloped, icosahe- • Persons who are sexually active with multiple dral nucleocapsid symmetry, spherical particles, partners 52-55 nm in diameter • Adult patients with Fanconi anemia • Nucleic acid: Circular, double-stranded DNA, 7.9 kb • HPV-infected persons exposed to sun or UV light in length with unidirectional transcription • Increased susceptibility in immune suppressed • Physicochemical properties: Sparse information; pre- patients sumably susceptible to 0.3% povidone-iodine, to polysulfated and polysulfanated compounds, and to Vector and Reservoir Involved: dilute solutions of sodium dodecyl sulfate; ether- resistant, acid-stable, and heat-stable • None Disease Name: Blood Phase: • Nongenital skin warts • One study found HPV DNA in PBMCs, serum, and • Epidermodysplasia verruciformis plasma of patients with cervical and neck cancers and • Anogenital warts (condylomas) in 3 of 19 (15%) PBMCs from healthy blood donors. • Nonmelanoma skin cancer • Cervical cancer Survival/Persistence in Blood Products: • Anogenital cancer, penile cancer • Unknown • Papillomas of respiratory tract, larynx, mouth, or con- junctiva that includes oral and laryngeal cancers Transmission by Blood Transfusion: Priority Level: • In a recent study of 57 HIV-infected children, seven of • Scientific/Epidemiologic evidence regarding blood eight who were HPV DNA positive had a history of safety: Theoretical blood and/or plasma derivative transfusion as the • Public perception and/or regulatory concern regard- cause of their HIV infection. ing blood safety: Absent • Bovine papillomavirus type 2 has been transmitted • Public concern regarding disease agent: through blood via intramuscular inoculations. Low/Moderate Cases/Frequency in Population: Background: • Over 100 HPV types have been identified, 13 of which • Stable in population have been strongly or moderately associated with cer- • Narrow host range restricted to sites with stratified vical cancer. squamous epithelia that are cornified (skin) or non- • 2-3% of women undergoing routine Pap smear have cornified (genital and nongenital mucosa) abnormal cytology, the majority of which is associ- • High risk types found most frequently in association ated with HPV. with cervical cancer • The peak prevalence is seen in women 15-25 years of • New disease associations have been recognized over age, which may be 25-40%, and then declines with time. increasing age. Common Human Exposure Routes: Incubation Period: • Infection of basal keratinocytes primarily through • Limited information because exposures are generally wounds or skin abrasions multiple and onset is insidious • Contact with infected tissue or contaminated objects • Autoinoculation from site to site Likelihood of Clinical Disease: • Sexual intercourse • Delivery through infected birth canal • Varies with the particular strain 136S TRANSFUSION Volume 49, August 2009 Supplement APPENDIX 2 Primary Disease Symptoms: • Not indicated because transfusion transmission has not been demonstrated. • The typical skin lesion, the wart, is easily recognized, • No sensitive or specific question is feasible. particularly when in its most common location, the hands or feet (plantar warts). Most spontaneously Laboratory Test(s) Available: regress. • No FDA-licensed blood donor screening test exists. • Anogenital warts are also easy to recognize but may • Tissue diagnosis is usually by nucleic acid hybridiza- be internal and only observed following an appropri- tion or extraction of DNA followed by NAT. Southern ate examination. These can be recurrent, sometimes blots of extracted DNA are the gold standard and painful, and difficult to treat but may spontaneously allow for subtyping. remit. • Electron microscopy for viral particles or immuno- • Cervical intraepithelial neoplasia and cervical cancer logic detection of viral capsid antigens has low sensi- are often asymptomatic and only detected on routine tivity. Detection in PBMCs is generally performed by examination, primarily after cervical cytology has PCR or nested PCR. been assessed. Symptoms, such as bleeding and pain, appear as the cancer expands and disseminates. Currently Recommended Donor Deferral Period: • Other symptoms depend on location of the papilloma • No FDA Guidance or AABB Standard exists. and can include vocal disturbances from laryngeal • There is no indication for deferral of individuals with papillomatosis, pulmonary dysfunction from respira- known HPV infection unless presenting with a defer- tory tract involvement, and local discomfort from oral rable malignancy. lesions. Impact on Blood Availability: Severity of Clinical Disease: • Agent-specific screening question(s): Not applicable • Generally benign, except that it can lead to cervical • Laboratory test(s) available: Not applicable and anal cancers (most common cause of these malig- Impact on Blood Safety: nancies), and benign papillomatosis can be debilitat- ing because of location (e.g., laryngeal disease). • Agent-specific screening question(s): Not applicable • Laboratory test(s) available: Not applicable Mortality: Leukoreduction Efficacy: • Highly dependent on genotype and whether cancer • Unknown, but if virus is carried in peripheral blood, it ensues. Mortality is low, even in cancer patients if is probably within PBMCs, and thus leukoreduction early methods of detection are employed. would be expected to have some impact. Chronic Carriage: Pathogen Reduction Efficacy for Plasma Derivatives: • Chronic infection is typical although there is late • This is a nonenveloped virus and thus would not be spontaneous clearance. However, chronic viremia is affected by solvent-detergent treatment. unlikely. HPV may be carried in WBCs that intermit- • No data from model viruses tently seed the blood stream. Other Preventive Measures: Treatment Available/Efficacious: • Pathogen reduction strategies based on inactivation of DNA should be effective. • There are a variety of treatments for disease caused by • A quadrivalent human papilloma vaccine (Gardasil, HPV, ranging from simple intralesional or parenteral MSD) is available against HPV types 6, 11, 16, and 18, interferon or destructive therapy for genital warts, to which cause 70% of cervical cancer cases and 90% of surgery, laser excision repair, cryotherapy, or chemo- genital warts cases. therapy for high-grade dysplasia for cervical infection or cervical cancer. Successful therapy is associated Suggested Reading: with the disappearance of HPV DNA. 1. Antonsson A, Karanfilovska S, Lindqvist PG, Hansson • Therapeutic vaccines have had only limited success. BG. General acquisition of human papillomavirus Agent-Specific Screening Question(s): infections of skin occurs in early infancy. J Clin Micro- biol 2003;41:2509-14. • No specific question is in use; some donors with HPV- 2. Bodaghi S, Wood LV, Roby G, Ryder C, Steinberg SM, associated cancer may be temporarily excluded by Zheng ZM. Could human papillomaviruses be spread current donor history questions. through blood? J Clin Microbiol 2005;43:5428-34. Volume 49, August 2009 Supplement TRANSFUSION 137S APPENDIX 2 3. de Villiers E, Fauquet C, Broker TR, Bernard HU, zur 5. Stocco dos Santos RC, Lindsey CJ, Ferraz OP,Pinto JR, Hausen H. Classification of papillomaviruses. Virol- Mirandola RS, Benesi FJ, Birgel EH, Pereira CA, Beçak ogy 2004;324:17-27. W. Bovine papillomavirus transmission and chromo- 4. Howley PM, Lowy DR. Papillomaviruses. In: Knipe somal aberrations: an experimental model. J Gen DM, Howley PM, editors. Fields virology, 5th ed. Virol 1998;79:2127-35. Philadelphia: Lippincott Williams & Wilkins; 2007. p. 2299-354. 138S TRANSFUSION Volume 49, August 2009 Supplement.