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Disease Categories > Infectious Disease > Viruses

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Human Papillomavirus - HPV

Human papilloma virus (HPV) is a common sexually transmitted virus.

Epidemiology

Prevalence – 20 million infected in U.S.
Age – peak age 15-30 years
Sex – F>M
Transmission – vaginal, oral, anal sex

Organism

DNA virus
Multiple genotypes (>100) of varying infectivity
HPV is the etiologic agent for most cases of cervical cancer
- >30 types are sexually transmitted

Pathophysiology

Most women infected with high-risk genital HPV, particularly women under 30 years of age, do not develop cancer
Immune response effectively clears the infection, usually within 2 years
Persistent infection with high-risk (HR) types of HPV
- Associated with increased risk for the presence of or future risk of developing high-grade dysplasia or cervical carcinoma
HPV is also a risk factor for anal carcinoma in select populations

Clinical Presentation

Frequently asymptomatic
May present with genital warts
Abnormal Pap smear

Diagnosis and Disease Monitoring

HPV co-testing with cervical cytology (Pap smear) is approved as a sensitive method of primary screening for cervical cancer in women over the age of 30

Treatment

Women with atypical squamous cells of undetermined significance (ASC-US) should be managed using a program of either repeat cervical cytology testing, immediate colposcopy or DNA testing for high-risk types of human papillomavirus (HPV)
- Reflex testing for HPV DNA
  - Preferred approach when liquid-based cytology is used for screening
- For HPV DNA negative, repeat cytologic testing at 12 months
- For HPV DNA positive, immediate colposcopy

Indications for Ordering

Tests generally appear in the order most useful for common clinical situations
Click on number for test-specific information in the ARUP Laboratory Test Directory

Test Name and Number	Recommended Use	Limitations	Follow Up
Human Papillomavirus (HPV) DNA Probe, High Risk, Cervical Brush (Digene) with Reflex to Genotyping 0060818 Method: Nucleic Acid Probe/Polymerase Chain Reaction	Digene Hybrid Capture 2 DNA Assay. This panel includes HPV high-risk genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 Used with cervical cytology samples (ThinPrep^® or SurePath) or the Digene Cervical Collection Kit Triage of ASC-US cervical cytology Follow-up of treated/untreated histologic CIN1 Follow-up of LSIL in adolescent females Can be used with anal-rectal cytology samples in some circumstances Determine “test of cure” following treatment (LEEP, Cone) for histologic-proven cervical abnormalities (CIN2,3/Ca)	False-negatives due to inadequate cellularity can occur Vaginal specimens are not recommended because of limited clinical correlative data Cross-reactions with other genotypes (e.g., low-risk) may occur Results should be correlated with cytologic/histologic findings	See 2001 Consensus Guidelines for the Management of Women with Cervical Cytologic Abnormalities in the "Guidelines" section of topic
Cytology, ThinPrep® Pap with Reflex to Human Papillomavirus (HPV) DNA Probe, High Risk 8100212 Method: ThinPrep® 2000 System/Routine Cytopathologic Evaluation/Nucleic Acid Probe	This panel includes ThinPrep^® liquid-based cytology (LBC) plus automatic reflex to high-risk HPV DNA testing when the results of the Pap test are atypical squamous cells of undetermined significance (ASC-US) The HPV testing is performed on residual material in the ThinPrep^® vial	False-negatives due to inadequate cellularity can occur Cross-reactions with other genotypes (e.g., low-risk) may occur Results should be correlated with cytologic/histologic findings	See 2001 Consensus Guidelines for the Management of Women with Cervical Cytologic Abnormalities in Guidelines section of topic
Human Papillomavirus (HPV) DNA Probe, High Risk SurePath® (AutoCyte) with Reflex to Genotyping 0060817 Method: Nucleic Acid Probe/Polymerase Chain Reaction	High-risk HPV test detects HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, which are associated with cervical cancer and its precursor lesions	Cross-reactions with other genotypes may occur Correlate results with cytology and histologic findings Sensitivity may be affected by cellularity of specimen
Human Papillomavirus (HPV) DNA Probe, High Risk ( ThinPrep®) with Reflex to Genotyping 0060816 Method: Nucleic Acid Probe/Polymerase Chain Reaction	The high-risk HPV test detects HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, which are associated with cervical cancer and its precursor lesions	Cross-reactions with other genotypes may occur Correlate results with cytology and histologic findings Sensitivity may be affected by cellularity of specimen
Cytology, SurePath™ Liquid-Based Pap Test (AutoCyte PREP™ System) with Reflex to Human Papillomavirus (HPV) DNA Probe, High Risk 8100214 Method: PrepStain™ Slide Processor/Routine Cytopathologic Evaluation/Nucleic Acid Probe	This panel includes SurePath LBC plus automatic reflex to high-risk HPV DNA testing when the results of the Pap test are atypical squamous cells of undetermined significance (ASC-US) The HPV test is performed on residual material from the SurePath processed sample	False-negatives due to inadequate cellularity can occur Cross-reactions with other genotypes (e.g., low-risk) may occur Results should be correlated with cytologic/histologic findings	See 2001 Consensus Guidelines for the Management of Women with Cervical Cytologic Abnormalities in Guidelines section of topic

Additional Tests Available

Click on number for test-specific information in the ARUP Laboratory Test Directory

Test Name and Number	Comments
Human Papillomavirus (HPV) Panel, Paraffin 8030622 Method: In situ Hybridization	This panel includes: Low-risk HPV (Genotypes: 6,11) and High-risk HPV (Genotypes: 16, 18, 31, 33, 35, 45, 51, 52, 56, 58, 66) Used to test formalin fixed, paraffin embedded (FFPE) tissue biopsy sample
Human Papillomavirus (HPV) Low Risk, Paraffin 8030623 Method: In situ Hybridization	Low-risk HPV (Genotypes: 6,11) Used to test formalin fixed, paraffin embedded (FFPE) tissue biopsy samples
Human Papillomavirus (HPV) High Risk, Paraffin 8030624 Method: In situ Hybridization	High-risk HPV (Genotypes: 16, 18, 31, 33, 35, 45, 51, 52, 56, 58, 66) Used to test formalin fixed, paraffin embedded (FFPE) tissue biopsy samples
Cytology, ThinPrep® Pap Test™ 8100211 Method: ThinPrep® 2000 System
Human Papillomavirus (HPV) DNA Probe, High Risk, Cervical Brush (Digene) 0065999 Method: Nucleic Acid Probe	Digene Hybrid Capture 2 DNA Assay. This panel includes HPV high-risk genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 Used with cervical cytology samples (ThinPrep^® or SurePath) or the Digene Cervical Collection Kit Triage of ASC-US cervical cytology Follow-up of treated/untreated histologic CIN1 Follow-up of LSIL in adolescent females Can be used with anal-rectal cytology samples in some circumstances Determine “test of cure” following treatment (LEEP, Cone) for histologic-proven cervical abnormalities (CIN2,3/Ca)
Human Papillomavirus (HPV) DNA Probe, High Risk Surepath® (AutoCyte) 0060744 Method: Nucleic Acid Probe	High-risk HPV test detects HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 56, 58, 59 and 68, which are associated with cervical cancer and its precursor lesions
Human Papillomavirus (HPV) DNA Probe, High Risk (ThinPrep®) 0060750 Method: Nucleic Acid Probe	The high-risk HPV test detects HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 56, 58, 59 and 68, which are associated with cervical cancer and its precursor lesions

Additional Information

A positive high-risk HPV test result indicates that the patient may be infected with one or more of the following HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68, which are associated with cervical cancer and its precursor lesions. However, cross-reactions with other genotypes may occur. Results should be correlated with cytologic/histologic findings.

A positive low-risk HPV test result indicates that the patient may be infected with 1 or more of the following HPV genotypes: genotypes 6 and 11.

Guidelines

Saslow D, Runowicz CD, Solomon D, Moscicki AB, Smith RA, Eyre HJ, Cohen C. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin. 2002;52(6):342-362. (Link to PubMed)

Screening for cervical cancer: recommendations and rationale. United States Preventive Services Task Force - Independent Expert Panel. 1996 (revised 2003 Jan 22). 21 pages. NGC:002758 (Link to NGC)

Solomon D, Davey D, Kurman R, Moriarty A, O'Connor D, Prey M, Raab S, Sherman M, Wilbur D, Wright T Jr, Young N. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002;287(16):2114-2119. (Link to PubMed)

Wright TC Jr, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA. 2002;287(16):2120-2129. (Link to PubMed)

Wright TC Jr, Schiffman M, Solomon D, Cox JT, Garcia F, Goldie S, Hatch K, Noller KL, Roach N, Runowicz C, Saslow D. Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening. Obstet Gynecol. 2004;103(2):304-309. (Link to PubMed)

General References

Gray W, Bayer-Pietsch E, Chieco P, Cochand Priollet B, Desai M, Drijkoningen M, Griffin M, Hagmar B, Kapila K, Kloboves-Prevodnik V, Kobayashi T, Krogerus L, Majak B, Mihailovici M, Olszewski W, Schenck U, Schmitt F, Shabalova I, Shapiro N, Smith J, Tani E, Totsch M, Vass L, Wiener H, Herbert A. The future of cytopathology in Europe. Will the wider use of HPV testing have an impact on the provision of cervical screening?. Cytopathology. 2007;18(5):278-282. (Link to PubMed)

Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;338(7):423-428. (Link to PubMed)

Ronco G, Giorgi-Rossi P, Carozzi F, Dalla Palma P, Del Mistro A, De Marco L, De Lillo M, Naldoni C, Pierotti P, Rizzolo R, Segnan N, Schincaglia P, Zorzi M, Confortini M, Cuzick J. Human papillomavirus testing and liquid-based cytology in primary screening of women younger than 35 years: results at recruitment for a randomised controlled trial. Lancet Oncol. 2006;7(7):547-555. (Link to PubMed)

Solomon D, Schiffman M, Tarone R. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst. 2001;93(4):293-299. (Link to PubMed)

Wentzensen N, von Knebel Doeberitz M. Biomarkers in cervical cancer screening. Dis Markers. 2007;23(4):315-330. (Link to PubMed)

Wright TC Jr, Cox JT, Massad LS, Carlson J, Twiggs LB, Wilkinson EJ. 2001 consensus guidelines for the management of women with cervical intraepithelial neoplasia. Am J Obstet Gynecol. 2003;189(1):295-304. (Link to PubMed)

References from the ARUP Institute for Clinical and Experimental Pathology®

Holladay EB, Logan S, Arnold J, Knesel B, Smith GD. A comparison of the clinical utility of p16(INK4a) immunolocalization with the presence of human papillomavirus by hybrid capture 2 for the detection of cervical dysplasia/neoplasia. Cancer. 2006;108(6):451-461. (Link to PubMed)

Layfield LJ, Qureshi MN. HPV DNA testing in the triage of atypical squamous cells of undetermined significance (ASCUS): cost comparison of two methods. Diagn Cytopathol. 2005;33(2):138-143. (Link to PubMed)

Renshaw AA, Mody DR, Walsh M, Bentz JS, Colgan TJ. The significance of certification in liquid-based cytology and performance in the college of american pathologists interlaboratory comparison program in cervicovaginal cytopathology. Arch Pathol Lab Med. 2006;130(9):1269-1272. (Link to PubMed)

Rowe LR, Aldeen W, Bentz JS. Prevalence and typing of HPV DNA by hybrid capture II in women with ASCUS, ASC-H, LSIL, and AGC on ThinPrep Pap tests. Diagn Cytopathol. 2004;30(6):426-432. (Link to PubMed)

Reviewed by

Collins, Brian T., M.D. Medical Director, Cytopathology at ARUP Laboratories; Professor, Pathology, University of Utah

Perkins, Sherrie L. , M.D., Ph.D. Medical Director, Hematopathology at ARUP Laboratories; Professor, Anatomic Pathology, University of Utah

Petti, Cathy A., M.D. Medical Director, Infectious Diseases at ARUP Laboratories; Assistant Professor, Pathology and Medicine, University of Utah

Comprehensive Review: May 2008
Last Update: May 2008