Human Papillomavirus - HPV

Key Points

HPV Testing in Women

  • Screening guidelines
  • Screening recommendations
    • Women under 21 years of age

      HPV Screening Recommendations for Women <21 Years of Age

      Screening method of choice

      Management of screen results

      No cervical cancer screening (cytology or HPV) regardless of risk factors

      N/A

      Women 21 to under 25 years

      HPV Screening Recommendations for Women 21-<25 Years of Age

      (Women 21 to under 25 years of age algorithm available)

      Screening method of choice

      Management of screen results

      Cytology (cytology alone or cytology with reflex)

      Note: SurePath cytology can only be used if Option 1 will be chosen for ASC-US cytology

      Normal cytology
      • Repeat cytology in 3 years

      ASC-US cytology

      • OPTION 1 – repeat cytology in 1 year
      • OPTION 2  – hrHPV testing (HPV TMA or HPV PCR)
        • HPV negative – return to routine screening (choice of screening based on age; do not initiate next testing until 3 years from last normal or negative test)
        • HPV positive – refer to ASCCP consensus guidelines (p. S10)

      LSIL or more severe cytology

      Do not use HPV testing for screening in women <25 years. HPV testing is only appropriate in women <25 years for triaging those with abnormal cytology.

      hrHPV = high-risk HPV; ASC-US = atypical squamous cells of undetermined significance; LSIL = low-grade squamous intraepithelial lesion

      Women 25 to under 30 years of age

      HPV Screening Recommendations for Women 25-<30 Years of Age

      (Women 25 to under 30 years of age algorithm available)

      Screening method of choiceManagement of screen results

      OPTION 1 – primary HPV testing (hrHPV with 16 and 18 genotype by PCR) for cervical cancer screening

      Note: client should retain aliquot for cytology testing in case of hrHPV positivity

      HPV type 16/18 positive – colposcopy

      Any of other 12 hrHPV positivecytology

      • ≥ASC-US – colposcopy
      • Negative for intraepithelial lesion or malignancy (NILM) – repeat cytology in 1 year

      HPV negative – routine screening (choice of screening based on age; do not initiate testing until 3 years from last normal or negative test)

      OPTION 2 – cytology (cytology alone or cytology with reflex)

      Note: SurePath cytology can only be used if Option 1 will be chosen for ASC-US cytology

      Normal cytology – repeat cytology in 3 years

      ASC-US cytology

      • OPTION 1 – repeat cytology in 1 year
      • OPTION 2 – hrHPV testing (HPV TMA or HPV PCR)
        • HPV negative – return to routine screening (choice of screening based on age; do not initiate next testing until 3 years from last normal or negative test)
        • HPV positive – refer to ASCCP consensus guidelines (p. S9)

      LSIL or more severe cytology

      hrHPV = high-risk HPV testing; ASC-US = atypical squamous cells of undetermined significance; NILM = negative for intraepithelial lesion or malignancy; LSIL = low-grade squamous intraepithelial lesion
      Women 30 to 65 years of age

      HPV Screening Recommendations for Women 30-65 Years of Age

      (Women 30 to 65 years of age algorithm available)

      Screening method of choice

      Management of screen results

      OPTION 1 – primary HPV testing (hrHPV with 16 and 18 genotype by PCR) for cervical cancer screening

      Note: client should retain aliquot for cytology testing in case of hrHPV positivity

      HPV type 16/18 positive colposcopy

      Any of other 12 hrHPV positive – cytology

      • ≥ASC-US – colposcopy
      • Negative for intraepithelial lesion or malignancy (NILM) – repeat cytology in 1 year

      HPV negative – routine screening (choice of screening based on age; do not initiate testing until 3 years from last normal or negative test)

      OPTION 2 – co-testing (HPV and cytology)

      Order co-testing bundled or cytology and HPV PCR testing individually

      Normal cytology and HPV negative

      • Repeat screening of choice at 5 years

      ASC-US cytology and HPV negative

      • Repeat screening of choice at 3 years

      Normal cytology and HPV positive

      • OPTION 1 – repeat co-testing in 1 year
      • OPTION 2 – hrHPV with 16 and 18 genotype by PCR
        • HPV type 16 /18 positive – colposcopy
        • Any of other 12 hrHPV positive – repeat co-testing in 1 year
        • HPV negative – repeat co-testing in 1 year

      ASC-US cytology and HPV positive

      LSIL or more severe cytology

      OPTION 3 – (cytology alone or cytology with reflex)

      Note: SurePath cytology can only be used if Option 1 will be chosen for ASC-US cytology

      Normal cytology

      • Repeat cytology in 3 years

      ASC-US cytology

      • OPTION 1 – repeat cytology in 1 year
      • OPTION 2 – hrHPV testing (HPV TMA or HPV PCR)
        • HPV negative – return to routine screening (choice of screening based on age; do not initiate next testing until 3 years from last normal or negative test)
        • HPV positive – refer to ASCCP consensus guidelines (p. S9)

      LSIL or more severe cytology

      hrHPV = high-risk HPV testing; ASC-US = atypical squamous cells of undetermined significance; NILM = negative for intraepithelial lesion or malignancy; LSIL = low-grade squamous intraepithelial lesion
      Women over 65 years of age

      HPV Screening Recommendations for Women >65 Years of Age

      (Women over 65 years of age algorithm available)

      Screening method of choice

      Management of screen results

      Prior screening was adequate and negative*No further screening

      Prior screening inadequate – perform co-testing (HPV and cytology)

      Order co-testing bundled or cytology and HPV PCR testing individually

      Normal cytology and HPV negative

      • Screen as per 30-65 year olds until adequate screening definition fulfilled

      ASC-US cytology and HPV negative

      Normal cytology and HPV positive

      • OPTION 1 – repeat co-testing in 1 year
      • OPTION 2 – hrHPV with 16 and 18 genotype by PCR specific detection
        • HPV type 16 /18 positive – colposcopy
        • Any of other 12 hrHPV positive – repeat co-testing in 1 year
        • HPV negative – repeat co-testing in 1 year

      ASC-US cytology and HPV positive

      LSIL or more severe cytology

      History of ≥CIN2+Use screening based on schedule for 30-65 year olds; screen for at least 20 years after positive CIN2 test

      *Adequate screening: 3 consecutive negative cytology results or 2 consecutive negative co-testing results within the last 10 years; most recent of either tests must be within the past 5 years

      hrHPV = high-risk HPV testing; ASC-US = atypical squamous cells of undetermined significance; NILM = negative for intraepithelial lesion or malignancy

      Post hysterectomy

      Screening method of choice

      Management of screen results

      No history of CIN2+

      No screening

      Post HPV vaccination

      Screening method of choice

      Management of screen results

      Use age-based screening recommendations in the tables above

      Use age-based recommendations in the tables above

  • HPV screening algorithms

HPV Testing in Men

  • Summary of recommendations
    • 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
    Source: http://www.cdc.gov/std/HPV/stdfact-hpv-and-men.htm

Diagnosis

Indications for Testing

Laboratory Testing

  • Refer to Key Points tab

Screening

  • Refer to Key Points tab

Clinical Background

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

Indications for Laboratory Testing

  • 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
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

A preferred test for cervical cancer screening co-testing option (5-year interval testing) in women ≥30 years

Triage women with equivocal and mildly abnormal cervical cytology

Follow-up for women treated for high-grade cervical intraepithelial neoplasia (CIN) to detect residual or recurrent cervical disease; order with cytology

 

Refer to Key Points tab

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

FDA-approved test for cervical cancer screening in combination with cervical cytology (Pap smear)

FDA-approved platform for primary HPV screening; client should retain aliquot for cytology testing in case of hrHPV positivity

Follow-up test in women ≥21 years with abnormal cytology results

Test amplifies DNA of HPV16, HPV18 and 12 hrHPV types associated with cervical cancer and its precursor lesions (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68)

 

Refer to Key Points tab

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

Use in conjunction with cytology (Pap smear) for primary cervical cancer screening in women ≥30 years

Knowledge of genotype is useful in triaging women to colposcopy who are cytology-negative (NILM) and HPV-positive

 

Refer to Key Points tab

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

A preferred routine cervical cancer screening test for women 21-<25 years

An acceptable test for women 25-65 years for 3-year screening intervals

For 5-year screening intervals, co-test (cytology and HPV) is preferred (eg, Cytology Thin Prep and HPV High Risk)

False-negative results may occur due to inadequate cellularity

Cross-reactions with other genotypes (eg, low-risk) may occur

Refer to Key Points tab

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

May be used for routine 3-year interval cervical cancer screening test in all women

For 5-year interval testing (co-testing) in women 30-65 years, order with HPV test (eg, Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification)

This is a screening test (moderate sensitivity), not a diagnostic test (low specificity)

SurePath sample medium for HPV testing is not FDA approved; SurePath medium may produce false-negative results under certain conditions (eg, when stability requirements are exceeded)

Refer to Key Points tab

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

An acceptable test for all women for 3-year interval cervical cancer screening

An acceptable test for cervical cancer screening co-testing option (5-year interval testing) in women 30-65 years when ordered in conjunction with HPV testing  (eg, Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification)

 

Refer to Key Points tab

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

A preferred test for cervical cancer screening co-testing option (5-year interval testing) in women ≥30 years when ordered in conjunction with cytology

Triage women with equivocal or mildly abnormal cervical cytology

Follow-up for women treated for high-grade cervical intraepithelial neoplasia (CIN) to detect residual or recurrent cervical disease; order with cytology

Detects  E6/E7 viral messenger RNA of the high-risk HPV genotypes associated with cervical cancer and its precursor lesions (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68)

Does not differentiate between types

Cross-reactivity with low-risk HPV genotypes 26, 67, 70, and 82 may occur

Sensitivity may be affected by specimen collection methods, stage of infection, and the presence of interfering substances

Refer to Key Points tab

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

FDA-approved test for cervical cancer screening in combination with cervical cytology (Pap smear) for women

Test amplifies DNA of 14 high-risk HPV types associated with cervical cancer and its precursor lesions (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68)

Does not include reflex to genotype

 

Refer to Key Points tab

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

Acceptable test for triaging women >30 years with negative cervical cytology (NILM Pap smear) and known positive HPV

Detects E6/E7 viral messenger RNA in only the high-risk HPV types 16, 18, and 45

Does not differentiate between types 18 and 45

Sensitivity may be affected by specimen collection methods, stage of infection, and the presence of interfering substances

Refer to Key Points tab

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

Use of FDA-cleared sample preservative (eg, ThinPrep) is recommended; refer to HPV, high risk with 16 and 18 genotype by PCR, ThinPrep OR HPV high risk by TMA with reflex to HPV genotypes 16 and 18/45 by TMA, ThinPrep

Test amplifies DNA of HPV16, HPV18 and 12 other high-risk HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) associated with cervical cancer and its precursor lesions

 

Refer to Key Points tab

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

Use of FDA-cleared sample preservative (ie, ThinPrep) is recommended; see HPV high risk testing

 

Refer to Key Points tab

Human Papillomavirus (HPV) 16 and 18 Genotype by PCR, SurePath 2011937
Method: Qualitative Polymerase Chain Reaction

Use of FDA-cleared sample preservative (ie, ThinPrep) is recommended; refer to HPV genotypes 16 and 18/45 by TMA, ThinPrep

Amplifies DNA of HPV16 and HPV18; provides genotyping

 

Refer to Key Points tab

Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Human Papillomavirus (HPV), High Risk by in situ Hybridization, Paraffin 2002899
Method: In situ Hybridization

In situ hybridization test to detect high-risk HPV subtypes in formalin-fixed, paraffin-embedded tissue

Detects high-risk genotypes associated with cervical cancer and precursor lesions (16, 18)

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

Preferred test is HPV high-risk in situ hybridization if determining potential cancer risk

Human Papillomavirus (HPV), High Risk by Hybrid Capture, ThinPrep 2008404
Method: Qualitative Nucleic Acid Probe

A preferred test for cervical cancer screening co-testing option (5-year interval testing) in women ≥30 years when ordered in conjunction with cytology

Triage women with equivocal and mildly abnormal cervical cytology

Follow-up for women treated for high-grade cervical intraepithelial neoplasia (CIN) to detect residual or recurrent cervical disease; order with cytology

Detects high-risk genotypes associated with cervical cancer and precursor lesions (16, 18; 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68)

Human Papillomavirus (HPV), High Risk by Hybrid Capture, Cervical Brush 0065999
Method: Qualitative Nucleic Acid Probe

An acceptable test for 3-year interval cervical cancer screening

Cannot use for cancer screening co-testing option (5-year interval testing) unless 2 specimens are submitted simultaneously (one is sent to cytology lab; the other is sent to HPV testing lab)

Triage women with equivocal and mildly abnormal cervical cytology

Follow-up for women treated for high-grade cervical intraepithelial neoplasia (CIN) to detect residual or recurrent cervical disease; order with cytology

Detects high-risk genotypes associated with cervical cancer and precursor lesions (16, 18; 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68)

Cytology, SurePath Liquid-Based Pap Test and Human Papillomavirus (HPV), High Risk by Hybrid Capture (for routine co-testing in women over 30) 2000133
Method: Microscopy/Qualitative Nucleic Acid Probe

Co-test for cervical cancer screening option (5-year interval testing) for women ≥30

Triage women with equivocal and mildly abnormal cervical cytology

Follow-up for women treated for high-grade cervical intraepithelial neoplasia (CIN) to detect residual or recurrent cervical disease; order with cytology

Available for University of Utah clients only

Cytology, SurePath Liquid-Based Pap Test with Reflex to Human Papillomavirus (HPV), High Risk by Hybrid Capture 2000135
Method: Microscopy/Qualitative Nucleic Acid Probe

A routine cervical cancer screening test for women 21-65 years; requires 3-year screening interval

Because this is a reflex test, triage HPV testing is performed only for abnormal cytology (ASC-US)

  • This test does not meet the requirements for co-testing (5-year interval testing, which requires both cytology and HPV testing)

For 5-year screening interval, co-testing (cytology and HPV) is preferred (eg, Cytology Thin Prep and HPV High Risk)

Human Papillomavirus (HPV), High Risk by Hybrid Capture, SurePath 0060744
Method: Qualitative Nucleic Acid Probe

When ordered in conjunction with cytology, this test is a co-testing option (5-year interval testing) in women ≥30 years

Triage women with equivocal and mildly abnormal cervical cytology

Follow-up for women treated for high-grade cervical intraepithelial neoplasia (CIN) to detect residual or recurrent cervical disease; order with cytology

SurePath sample medium for HPV testing is not FDA approved; SurePath medium may produce false-negative results under certain conditions (eg, when stability requirements are exceeded)