Human Papillomavirus - HPV

Cervical Cancer

  • Key Points
  • Diagnosis
  • Algorithms
  • Screening
  • Background
  • Lab Tests
  • References
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Human Papillomavirus Testing in Women

Screening Guidelines

  • ARUP Laboratories’ Cervical Cancer and HPV Screening Tests

    Screening Guidelines for the Prevention and Early Detection of Cervical Cancer (ACS/ASCCP/ASCP, 2012)

    HPV Testing in Men

    • Summary of recommendations (CDC, 2017)
      • Screening for anal cancer is not routinely recommended for men
        • HPV testing is not currently recommended for anal cancer screening
        • No HPV test is approved by the FDA for testing of men
        • Some experts recommend yearly anal cancer screening by cytology ("anal Pap") for homosexual, bisexual, and HIV-positive men (anal cancer is more common in these populations)
      • HPV is associated with the development of penile cancer
        • Screening tests are not available for penile cancer​

    HPV Testing in Head and Neck Cancer

    Refer to Head and Neck Cancer topic for information regarding oropharyngeal specimen testing

    Indications for Testing

    Laboratory Testing

    • Refer to Key Points section

    Refer to Key Points section

    Human papillomavirus (HPV) is the most common sexually transmitted viral infection.

    Epidemiology

    • Incidence – 20 million currently infected in the U.S.
    • Transmission – sexual contact (vaginal, oral, anal)

    Organism

    • DNA virus
    • Multiple genotypes (>100) of varying infectivity
      • >30 types are sexually transmitted
    • Etiologic agent for most cases of cervical cancer

    Pathophysiology

    • Persistent infection with oncogenic (high-risk) HPV genotypes associated with increased risk for developing high-grade dysplasia and cervical, vulvar, or vaginal carcinoma
    • Most women infected with high-risk genital HPV do not develop cancer; they clear the infection, usually within 2 years

    Clinical Presentation

    • Frequently asymptomatic
    • Abnormal Pap smear
    • Complications – cervical, vaginal, vulvar carcinoma

    Prevention

    • HPV vaccine – recommended for males and females 9-26 years in 3 doses
    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.

    Human Papillomavirus (HPV), High Risk with 16 and 18 Genotype by PCR, ThinPrep 2011940
    Method: Qualitative Polymerase Chain Reaction

    Follow-up 

    Refer to Key Points section

    Human Papillomavirus (HPV), High Risk by Transcription-Mediated Amplification (TMA) with Reflex to HPV Genotypes 16 and 18/45 by TMA, ThinPrep 2007890
    Method: Qualitative Transcription-Mediated Amplification

    Follow-up 

    Refer to Key Points section

    Human Papillomavirus (HPV), High Risk by Transcription-Mediated Amplification (TMA), ThinPrep 2007893
    Method: Qualitative Transcription-Mediated Amplification

    Follow-up 

    Refer to Key Points section

    Human Papillomavirus (HPV), High Risk by PCR, ThinPrep 2011947
    Method: Qualitative Polymerase Chain Reaction

    Follow-up 

    Refer to Key Points section

    Human Papillomavirus (HPV) Genotypes 16 and 18/45 by Transcription-Mediated Amplification (TMA), ThinPrep 2007894
    Method: Qualitative Transcription-Mediated Amplification

    Follow-up 

    Refer to Key Points section

    Human Papillomavirus (HPV), High Risk with 16 and 18 Genotype by PCR, SurePath 2011933
    Method: Qualitative Polymerase Chain Reaction

    Follow-up 

    Refer to Key Points section

    Human Papillomavirus (HPV), High Risk by PCR, SurePath 2011942
    Method: Qualitative Polymerase Chain Reaction

    Follow-up 

    Refer to Key Points section

    Cytology, ThinPrep Pap Test and Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification (TMA) (for routine co-testing in women over 30) 2000136
    Method: Microscopy/Qualitative Transcription-mediated Amplification

    Limitations 

    Test has an inherent false-negative rate

    Follow-up 

    Refer to Key Points section

    Cytology, SurePath Liquid-Based Pap Test and Human Papillomavirus (HPV), High Risk by PCR, SurePath (for routine co-testing in women over 30) 2000133
    Method: Microscopy/Qualitative Polymerase Chain Reaction

    Limitations 

    Test has an inherent false-negative rate

    Human Papillomavirus (HPV), High Risk by in situ Hybridization, Paraffin 2002899
    Method: In situ Hybridization

    Human Papillomavirus (HPV) Low Risk by in situ Hybridization, Paraffin 2002896
    Method: In situ Hybridization

    Cytology, SurePath Liquid-Based Pap Test 2000134
    Method: Microscopy

    Limitations 

    Test has an inherent false-negative rate

    Follow-up 

    Refer to Key Points section

    Cytology, ThinPrep Pap Test 2000137
    Method: ThinPrep 2000 System/Routine Cytopathologic Evaluation

    Limitations 

    Test has an inherent false-negative rate

    Follow-up 

    Refer to Key Points section

    Cytology, ThinPrep Pap Test with Reflex to Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification (TMA) 2000138
    Method: Microscopy/Qualitative Transcription-mediated Amplification

    Limitations 

    Test has an inherent false-negative rate

    Follow-up 

    Refer to Key Points section

    Cytology, SurePath Liquid-Based Pap Test with Reflex to Human Papillomavirus (HPV), High Risk by PCR, SurePath 2000135
    Method: Microscopy/ Qualitative Polymerase Chain Reaction

    Guidelines

    Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Jun 2017]

    Committee on Practice Bulletins—Gynecology. Practice Bulletin No. 168: Cervical Cancer Screening and Prevention. Obstet Gynecol. 2016; 128(4): e111-30. PubMed

    Huh WK, Ault KA, Chelmow D, Davey DD, Goulart RA, Garcia FA, Kinney WK, Massad S, Mayeaux EJ, Saslow D, Schiffman M, Wentzensen N, Lawson HW, Einstein MH. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Gynecol Oncol. 2015; 136(2): 178-82. PubMed

    Massad S, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, Solomon D, Wentzensen N, Lawson HW, 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013; 121(4): 829-46. PubMed

    Moyer VA, U.S. Preventive Services Task Force. Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012; 156(12): 880-91, W312. PubMed

    Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J, Garcia FA, Moriarty AT, Waxman AG, Wilbur DC, Wentzensen N, Downs LS, Spitzer M, Moscicki A, Franco EL, Stoler MH, Schiffman M, Castle PE, Myers ER, American Cancer Society, American Society for Colposcopy and Cervical Pathology, American Society for Clinical Pathology. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. Am J Clin Pathol. 2012; 137(4): 516-42. PubMed

    Sawaya GF, Kulasingam S, Denberg TD, Qaseem A, Clinical Guidelines Committee of American College of Physicians. Cervical Cancer Screening in Average-Risk Women: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2015; 162(12): 851-9. PubMed

    Smith RA, Manassaram-Baptiste D, Brooks D, Doroshenk M, Fedewa S, Saslow D, Brawley OW, Wender R. Cancer screening in the United States, 2015: a review of current American cancer society guidelines and current issues in cancer screening. CA Cancer J Clin. 2015; 65(1): 30-54. PubMed

    Summary of Recommendations for Clinical Preventive Services. American Academy of Family Physicians. Leawood, KS [Updated Jan 2017; Accessed: Mar 2017]

    Wright TC, Massad S, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D, 2006 American Society for Colposcopy and Cervical Pathology-sponsored Consensus Conference. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol. 2007; 197(4): 346-55. PubMed

    General References

    Arbyn M, Roelens J, Cuschieri K, Cuzick J, Szarewski A, Ratnam S, Reuschenbach M, Belinson S, Belinson JL, Monsonego J. The APTIMA HPV assay versus the Hybrid Capture 2 test in triage of women with ASC-US or LSIL cervical cytology: a meta-analysis of the diagnostic accuracy. Int J Cancer. 2013; 132(1): 101-8. PubMed

    Jarboe EA, Hunt JP, Layfield LJ. Cytomorphologic diagnosis and HPV testing of metastatic and primary oropharyngeal squamous cell carcinomas: a review and summary of the literature. Diagn Cytopathol. 2012; 40(6): 491-7. PubMed

    Laudadio J. Human papillomavirus detection: testing methodologies and their clinical utility in cervical cancer screening. Adv Anat Pathol. 2013; 20(3): 158-67. PubMed

    Pyne MT, Hamula CL, Tardif K, Law C, Schlaberg R. High-risk HPV detection and genotyping by APTIMA HPV using cervical samples. J Virol Methods. 2015; 221: 95-9. PubMed

    Schiffman M, Solomon D. Clinical practice. Cervical-cancer screening with human papillomavirus and cytologic cotesting. N Engl J Med. 2013; 369(24): 2324-31. PubMed

    Solomon D, Papillo JL, Davey DD, Cytopathology Education and Technology Consortium. Statement on HPV DNA test utilization. Am J Clin Pathol. 2009; 131(6): 768-9; discussion 770-3. PubMed

    Wentzensen N, Doeberitz Mv. Biomarkers in cervical cancer screening. Dis Markers. 2007; 23(4): 315-30. PubMed

    References from the ARUP Institute for Clinical and Experimental Pathology®

    Erali M, Pattison DC, Wittwer CT, Petti CA. Human papillomavirus genotyping using an automated film-based chip array. J Mol Diagn. 2009; 11(5): 439-45. PubMed

    Holladay B, Logan S, Arnold J, Knesel B, Smith D. 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): 451-61. PubMed

    Layfield LJ, Qureshi N. HPV DNA testing in the triage of atypical squamous cells of undetermined significance (ASCUS): cost comparison of two methods. Diagn Cytopathol. 2005; 33(2): 138-43. PubMed

    Pyne MT, Hamula CL, Tardif K, Law C, Schlaberg R. High-risk HPV detection and genotyping by APTIMA HPV using cervical samples. J Virol Methods. 2015; 221: 95-9. PubMed

    Pyne MT, Law C, Hillyard DR, Schlaberg R. Testing and genotyping of high-risk human papillomavirus by the cobas HPV Test and the Hybrid Capture 2 high-risk HPV DNA test using cervical and vaginal samples. J Clin Microbiol. 2014; 52(5): 1720-3. PubMed

    Renshaw AA, Mody DR, Walsh M, Bentz JS, Colgan TJ, Cytopathology Resource Committee, College of American Pathologists. 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): 1269-72. 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): 426-32. PubMed

    Tardif KD, Pyne MT, Malmberg E, Lunt TC, Schlaberg R. Cervical Cytology Specimen Stability in Surepath Preservative and Analytical Sensitivity for HPV Testing with the cobas and Hybrid Capture 2 Tests. PLoS One. 2016; 11(2): e0149611. PubMed

    Tardif KD, Simmon KE, Kommedal O, Pyne MT, Schlaberg R. Sequencing-based genotyping of mixed human papillomavirus infections by use of RipSeq software. J Clin Microbiol. 2013; 51(4): 1278-80. PubMed

    Wilson AR, Welch RJ, Hashibe M, Greenwood J, Jackson B, She RC. Surveillance of human papilloma virus using reference laboratory data for the purpose of evaluating vaccine impact. Online J Public Health Inform. 2014; 6(3): e194. PubMed

    Witt BL, Factor RE, Jarboe EA, Layfield LJ. Negative loop electrosurgical cone biopsy finding following a biopsy diagnosis of high-grade squamous intraepithelial lesion: frequency and clinical significance. Arch Pathol Lab Med. 2012; 136(10): 1259-61. PubMed

    Medical Reviewers

    Content Reviewed: 
    July 2017

    Last Update: September 2017