Human Papillomavirus (HPV) Detection, High-Risk Types
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Human papillomaviruses (HPV) are composed of an icosahedral viral particle (virion) containing an 8,000 base-pair double-stranded, circular DNA molecule surrounded by a protein capsid.
HPV infections are sexually transmitted. The presence of HPV in the female genital tract is associated with a number of disease states including genital condyloma acuminata, condyloma plana, bowenoid papulosis, and cervical, vaginal, and vulvar intraepithelial neoplasia and carcinoma.
Numerous types of HPV viruses have been identified by molecular analysis. These HPV types also can be categorized into low-, intermediate-, and high-risk groups based on their relative distribution in various histopathological diagnosis categories. Detection of high-risk genotypes (n=13) from genital specimens is considered a major determinant associated with the development of cervical cancer.(1-3) Historically, HPV 16 and HPV 18 have been regarded as high-risk cancer-associated HPVs; HPV types 6 and 11 as low-risk; and HPV types 31, 33, and 35 have been demonstrated to have an intermediate association with cancer. Despite this useful conceptual framework, these 7 HPV types have been found in only about 70% of cervical neoplasms. Additional HPVs including types 42, 43, 44, 45, 51, 52, 56, 58, 59, and 68 have been identified as the principal HPVs detected in the remaining lesions. HPV DNA also is present in approximately 10% of women with normal cervical epithelium, but the actual prevalence is strongly influenced by age and other demographic variables.
Prospective studies have shown that 15% to 28% of HPV DNA-positive women developed squamous intraepithelial neoplasia within 2 years, compared to only 1% to 3% of HPV DNA-negative women. In particular, the risk of progression for HPV types 16 and 18 was greater (approximately 40%) than for other HPV types.
Patients who are positive for a high-risk HPV type may be referred for colposcopy. For patients with "atypical squamous cells of unknown significance" (ASCUS) on Pap smear, HPV typing may be used to determine the need for colposcopy.(5-7) Patients who are negative may be followed according to the usual clinical practice.
While certain HPV types are strongly associated with cervical cancer, there is clear evidence that cofactors are involved. The nature and roles of these cofactors are under intense study; however, their contributions to malignant progression are still poorly understood. Some of the cofactors thought to interact with cancer-associated HPV types in the genesis of cervical malignancy are the herpes viruses, tobacco products, oral contraceptives, and certain dietary factors.
Detection of high-risk genotypes associated with the development of cervical cancer (3,4)
As an aid to triaging women with abnormal Pap smear results
A positive result indicates the presence of human papillomavirus (HPV) DNA due to 1 or more of the following genotypes of the virus: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. A negative result indicates the absence of HPV DNA of the target genotypes.
For patients with ASCUS Pap smear results and positive for high-risk HPV types, consider referral for colposcopy if clinically indicated.(5-7)
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not recommended for evaluation of suspected sexual abuse.
The prevalence of human papillomavirus (HPV) infection in a population may affect performance; positive predictive values decrease in populations with high prevalence of individuals with low-risk of infection.
A negative result does not exclude the possibility of HPV infection (eg, sampling errors may cause false-negative results).
If high concentrations of antifungal cream, contraceptive jelly, or douche are present when the specimen is collected, false-negative results may be obtained, especially if the specimen contains HPV DNA levels near the assay cutoff.
Specimens containing glacial acetic acid are inappropriate for testing and should not be submitted.
This test can only be used with cervical specimens collected using a broom-type collection device and placed in Cytic ThinPrep Pap Test PreservCyt Solution, or cervical specimens collected using SurePath.
Cross-reactivity between both HC2 HPV DNA test probes and the bacterial plasmid pBR322 is possible and the presence of pBR322 homologous sequences has been reported in human genital specimens. False-positive results could occur in the presence of high levels of bacterial plasmid.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Negative for types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Sanclemente G, Gill DK: Human papillomavirus molecular biology and pathogenesis. J Eur Acad Dermatol Venereol 2001;16(3):231-240
2. Castle PE, Wacholder S, Lorincz AT, et al: A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women. J Natl Cancer Inst 2002;94(18):1406-1414
3. Brentjens MH, Yeung-Yue KA, Lee PC, Tyring SK: Human papillomavirus: a review. Dermatol Clin 2002;20(2):315-331
4. Hagensee ME: Infection with human papillomavirus: update on epidemiology, diagnosis treatment. Curr Infect Dis Rep 2000;2(1):18-24
5. Nguyen HN, Nordqvist SR: The bethesda system and evaluation of abnormal pap smears. Semin Surg Oncol 1999;16(3):217-221
6. Wright TC Jr, Cox JT, Massad LS: 2001 consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 2002;287(16):2120-2129
7. Crum CP, Berkowitz RS: Human papillomaviruses. Applications, caveats and prevention. J Reprod Med 2002;47(7):519-528