Human Papillomavirus

Clinical Background

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

See Also

Cervical Cancer

Sexually Transmitted Infections, Bacteria

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Human Papillomavirus (HPV) DNA Probe, High Risk, Cervical Brush (Digene) with Reflex to Genotyping

ARUP #: 0060818

Methodology: Nucleic Acid Probe/Polymerase Chain Reaction

Use:

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)

Limitations:

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

Follow-up:

See 2001 Consensus Guidelines for the Management of Women with Cervical Cytologic Abnormalities in the "Guidelines" section of topic

Test name: Cytology, ThinPrep® Pap with Reflex to Human Papillomavirus (HPV) DNA Probe, High Risk

ARUP #: 8100212

Methodology: ThinPrep® 2000 System/Routine Cytopathologic Evaluation/Nucleic Acid Probe

Use:

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

Limitations:

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

Follow-up:

See 2001 Consensus Guidelines for the Management of Women with Cervical Cytologic Abnormalities in Guidelines section of topic

Test name: Human Papillomavirus (HPV) DNA Probe, High Risk SurePath® (AutoCyte) with Reflex to Genotyping

ARUP #: 0060817

Methodology: Nucleic Acid Probe/Polymerase Chain Reaction

Use:

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

Limitations:

Cross-reactions with other genotypes may occur

Correlate results with cytology and histologic findings

Sensitivity may be affected by cellularity of specimen

Test name: Human Papillomavirus (HPV) DNA Probe, High Risk ( ThinPrep®) with Reflex to Genotyping

ARUP #: 0060816

Methodology: Nucleic Acid Probe/Polymerase Chain Reaction

Use:

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

Limitations:

Cross-reactions with other genotypes may occur

Correlate results with cytology and histologic findings

Sensitivity may be affected by cellularity of specimen

Test name: Cytology, SurePath™ Liquid-Based Pap Test (AutoCyte PREP™ System) with Reflex to Human Papillomavirus (HPV) DNA Probe, High Risk

ARUP #: 8100214

Methodology: PrepStain™ Slide Processor/Routine Cytopathologic Evaluation/Nucleic Acid Probe

Use:

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

Limitations:

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

Follow-up:

See 2001 Consensus Guidelines for the Management of Women with Cervical Cytologic Abnormalities in Guidelines section of topic

Additional Tests Available

Test name: Human Papillomavirus (HPV) Panel, Paraffin

ARUP #: 8030622

Methodology: In situ Hybridization

Comments: 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

Test name: Human Papillomavirus (HPV) Low Risk, Paraffin

ARUP #: 8030623

Methodology: In situ Hybridization

Comments: Low-risk HPV (Genotypes: 6,11)Used to test formalin fixed, paraffin embedded (FFPE) tissue biopsy samples

Test name: Human Papillomavirus (HPV) High Risk, Paraffin

ARUP #: 8030624

Methodology: In situ Hybridization

Comments: 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

Test name: Cytology, ThinPrep® Pap Test™

ARUP #: 8100211

Methodology: ThinPrep® 2000 System

Comments:

Test name: Human Papillomavirus (HPV) DNA Probe, High Risk, Cervical Brush (Digene)

ARUP #: 0065999

Methodology: Nucleic Acid Probe

Comments: 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 68Used with cervical cytology samples (ThinPrep® or SurePath) or the Digene Cervical Collection KitTriage of ASC-US cervical cytologyFollow-up of treated/untreated histologic CIN1Follow-up of LSIL in adolescent femalesCan be used with anal-rectal cytology samples in some circumstancesDetermine “test of cure” following treatment (LEEP, Cone) for histologic-proven cervical abnormalities (CIN2,3/Ca)

Test name: Human Papillomavirus (HPV) DNA Probe, High Risk Surepath® (AutoCyte)

ARUP #: 0060744

Methodology: Nucleic Acid Probe

Comments: 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

Test name: Human Papillomavirus (HPV) DNA Probe, High Risk (ThinPrep®)

ARUP #: 0060750

Methodology: Nucleic Acid Probe

Comments: 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.

References

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.

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

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.

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.

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.

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.

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.

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.

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.

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

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.

References from the ARUP Institute for Clinical and Experimental Pathology Research®

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.

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.

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.

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.

Medical Reviewers

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