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Test ID: HPV Human Papillomavirus (HPV) DNA Detection with Genotyping, High-Risk Types by PCR, ThinPrep, Varies

Reporting Name

HPV with Genotyping, PCR, ThinPrep

Useful For

Detection of high-risk (HR) genotypes associated with the development of cervical cancer

 

Aids in triaging women with abnormal Pap smear results

 

Individual genotyping of human papillomavirus (HPV)-16 and/or HPV-18, if present

 

Results of HPV-16 and HPV-18 genotyping can aid in triaging women with positive HR-HPV but negative Pap smear results

 

This test is not recommended for evaluation of suspected sexual abuse.

 

This test is not intended for use in determining the need for treatment (ie, excisional or ablative treatment of the cervix) in the absence of high-grade cervical dysplasia. Patients who are HPV16/18 positive should be monitored carefully for the development of high-grade cervical dysplasia according to current practice guidelines.

 

This test is not intended for women who have undergone hysterectomy.

 

This test is not intended for use with samples other than those collected by a clinician using an endocervical brush or spatula and placed in the ThinPrep Pap test PreservCyt solution.

Clinical Information

Persistent infection with human papillomavirus (HPV) is the principal cause of cervical cancer. The presence of HPV has been implicated in more than 99% of cervical cancers worldwide, including both cervical squamous cell carcinoma and cervical adenocarcinoma. Before the development of invasive cancer, HPV infects the squamous mucosa cells and/or the glandular cells of the endocervix, leading to clonal expansion and morphologic changes. While the HPV-infected cells are restricted to their normal anatomic location, these changes are classified as cervical intraepithelial neoplasia (CIN). The severity of the morphologic changes and the degree to which those changes resemble the morphology of an invasive carcinoma are used to "grade" CIN. In general, high-grade CIN more closely resembles invasive carcinoma morphologically. HPV can also infect other mucosal cells in the anogenital region, such as the vaginal mucosa, leading to the development of HPV-associated intraepithelial neoplasia as well as invasive carcinoma not involving the cervix itself, although this is less common.

 

HPV is a small, nonenveloped, double-stranded DNA virus, with a genome of approximately 8,000 nucleotides. There are more than 118 different types of HPV and approximately 40 different HPVs can infect the human anogenital mucosa. Only a very small percentage of patients who are exposed to HPV will develop CIN. Of those patients who develop CIN, only a small percentage will progress to invasive cervical cancer. Sexually transmitted infection with HPV is extremely common, with estimates of up to 75% of all women being exposed to HPV at some point. However, almost all infected women will mount an effective immune response and clear the infection within 2 years without any long-term health consequences. Both high-risk HPV genotypes (especially HPV-16 and 18), as well as persistent HPV infection (eg, an infection that is not cleared by the patient's immune system over time), are associated with an increased chance of progressing to high-grade CIN and invasive cancer.

 

Data suggest that certain HPV genotypes types (eg, HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) are considered high-risk (HR) for the development of cervical cancer and its precursor lesions. Furthermore, HPV types 16 and 18 have been regarded as the genotypes most closely associated with progression to cervical cancer. HPV-16 is the most carcinogenic, and is associated with approximately 60% of all cervical cancers, while HPV-18 accounts for approximately 10% to 15% of cervical cancers.(1-3)

 

In developed countries with cervical cancer screening programs, the Pap smear has been used since the mid-1950s as the primary tool to morphologically detect CIN, the precursor to cervical cancer. Pap smear screening has decreased death rates due to cervical cancer dramatically, since in many cases CIN can be treated and eliminated (eg, by local excision) before it progresses to invasive carcinoma. Although Pap smears and other liquid-based cytology methods have many advantages, they also have limitations: they require subjective interpretation by a highly trained cytopathologist and misinterpretation can occur, morphologic changes that resemble HIV-associated CIN can be caused by other conditions (eg, inflammation), and Pap smear does not sample every cell within the cervix/anogenital region potentially leading to falsely negative results. Perhaps most importantly, Pap smear does not differentiate between HPV genotypes that are high or low risk for progression to cervical cancer and it does not detect very early infections, which may lack a morphological phenotype.

 

Nucleic acid (DNA) testing by polymerase chain reaction (PCR) has become a standard, noninvasive method for determining the presence of a cervical HPV infection. Proper implementation of nucleic acid testing for HPV may:

1. Increase the sensitivity of cervical cancer screening programs by detecting high-risk lesions earlier in women 30 years and older with normal cytology

2. Reduce the need for unnecessary colposcopy and treatment in patients 21 and older with cytology results showing atypical squamous cells of undetermined significance (ASC-US)

 

Recently, data suggest that individual genotyping for HPV types 16 and 18 can assist in determining appropriate follow-up testing and triaging women at risk for progression to cervical cancer. Studies have shown that the absolute risk of CIN-2 or worse in HPV-16 and/or HPV-18 positive women is 11.4% (95% confidence interval [CI] 8.4%-14.8%) compared with 6.1% (95% CI, 4.9%-7.2%) of women positive for other HR-HPV genotypes, and 0.8% (95% CI, 0.3%-1.5%) in HR-HPV-negative women.(4) Based in part on these data, the American Society for Colposcopy and Cervical Pathology (ASCCP) now recommends that HPV 16/18 genotyping be performed on women who are positive for HR-HPV but negative by routine cytology. Women who are found to be positive for HPV-16 and/or -18 may be referred to colposcopy, while women who are negative for genotypes 16 and 18 may have repeat cytology and HR-HPV testing in 12 months.(1)

Interpretation

A positive result indicates the presence of human papillomavirus (HPV) DNA due to 1 or more of the following genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68.

 

A negative result indicates the absence of HPV DNA of the targeted genotypes.

 

For patients with atypical squamous cells of undetermined significance (ASC-US) Pap smear result and who are positive for high-risk (HR) HPV, consider referral for colposcopy, if clinically indicated.

 

For women aged 30 years and older with a negative Pap smear result but who are positive for HPV-16 and/or HPV-18, consider referral for colposcopy, if clinically indicated.

 

For women aged 30 years and older with a negative Pap smear, positive-HR-HPV test result, but who are negative for HPV-16 and HPV-18, consider repeat testing by both cytology and a HR-HPV test in 12 months.

Report Available

3 to 6 days

Day(s) Performed

Monday through Friday

Clinical Reference

1. Saslow D, Solomon D, Lawson HW, et al: 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. J Low Genit Tract Dis. 2012;16(3):175-204. doi: 10.1097/LGT.0b013e31824ca9d5.  

2. Walboomers JM, Jacobs MV, Manos MM, et al: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12-19. doi: 10.1002/(SICI)1096-9896(199909)189:1

3. de Sanjose S, Quint WG, Alemany L, et al: Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11:1048-1056. doi: 10.1016/S1470-2045(10)70230-8.

4. Wright TC Jr, Stoler MH, Sharma A, et al: Evaluation of HPV-16 and HPV-18 genotyping for the triage of women with high-risk HPV positive, cytology-negative results. Am J Clin Pathol. 2011 Oct;136(4):578-586. doi: 10.1309/AJCPTUS5EXAS6DKZ.

Method Name

Real-Time Polymerase Chain Reaction (PCR)

Specimen Type

Varies


Necessary Information


Specimen source is required.



Specimen Required


Submit only 1 of the following specimens:

 

Specimen Type: Cervical (endocervical or ectocervical)

Container/Tube: ThinPrep/PreservCyt solution vial

Specimen Volume: 3 mL of solution in ThinPrep/PreservCyt vial

Collection Instructions:

1. Bag ThinPrep specimens individually as they have a tendency to leak during transport.

2. Place labels on the vial and on the bag.

 

Specimen Type: Vaginal

Container/Tube: ThinPrep/PreservCyt solution vial

Specimen Volume: 3 mL of solution in ThinPrep/PreservCyt vial

Collection Instructions:

1. Bag ThinPrep specimens individually as they have a tendency to leak during transport.

2. Place labels on the vial and on the bag.

Additional Information: This assay is validated but not FDA-approved for vaginal source specimens.


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Ambient (preferred) 42 days
  Refrigerated  42 days

Reference Values

Negative for human papillomavirus (HPV) genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68

Test Classification

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information

87624

G0476 (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
HPV HPV with Genotyping, PCR, ThinPrep 77378-8

 

Result ID Test Result Name Result LOINC Value
SS017 Specimen Source 31208-2
35924 HPV High Risk type 16, PCR 61372-9
35925 HPV High Risk type 18, PCR 61373-7
35926 HPV other High Risk types, PCR 77375-4

Forms

If not ordering electronically, complete, print, and send Microbiology Test Request (T244) with the specimen.

Mayo Clinic Laboratories | Microbiology and Infectious Disease Catalog Additional Information:

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