Human Papillomavirus - HPV

Cervical Cancer

Primary Author: Schlaberg, Robert, MD, MPH.

Human Papillomavirus Testing in Women

Screening Guidelines

Current cervical cancer screening guidelines

American Cancer Society (ACS), American Society for Colposcopy and Cervical Pathology (ASCCP), Amercian Society for Clinical Pathology (ASCP) Screening Guidelines for the Prevention and Early Detection of Cervical Cancer (Saslow, 2012)
- Cervical Cancer Screening Recommendations (ASCCP PowerPoint, 2012)
- ASCCP updated disease management guidelines (includes links to algorithms and FAQs) (Massad, 2013)
Comparison of screening guidelines for average-risk women (CDC, 2015; includes interim guidance for primary high-risk human papillomavirus [hrHPV] testing)

Primary high-risk human papillomavirus (hrHPV) testing

Recent guidance from the Society of Gynecologic Oncology (SGO)/ASCCP (2015), motivated by FDA’s approval of an hrHPV test as a primary test performed for cervical cancer screening, suggests that primary hrHPV testing can be considered for women starting at age 25
Use of primary high-risk human papillomavirus testing for cervical cancer screening: Interim clinical guidance (Huh, 2015)

Low-risk HPV

No clinical role for testing for low-risk HPV in cervical cancer screening or in the evaluation of women with abnormal cytology (Choosing Wisely, American Society of Clinical Pathology, 2016)

ARUP Laboratories’ Cervical Cancer and HPV Screening Tests

Primary HPV testing (FDA approved in women ≥25 years)

Media	Test Number	Test Name	Use
ThinPrep	2011940^a	Human Papillomavirus (HPV), High Risk with 16 and 18 Genotype by PCR, ThinPrep	FDA-approved platform for primary HPV screening in women ≥25 years FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) in women ≥30 years Follow-up test for abnormal cytology results in women ≥21 years 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
^aGenotype testing – determines presence of high-risk genotype (16 or 18) For collection information, refer to ARUP Laboratories’ Test Directory (available by clicking on each test number above)

Media

Test Number

Test Name

Use

ThinPrep

2011940^a

Human Papillomavirus (HPV), High Risk with 16 and 18 Genotype by PCR, ThinPrep

FDA-approved platform for primary HPV screening in women ≥25 years
FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) in women ≥30 years
Follow-up test for abnormal cytology results in women ≥21 years
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

^aGenotype testing – determines presence of high-risk genotype (16 or 18)

For collection information, refer to ARUP Laboratories’ Test Directory (available by clicking on each test number above)

HPV testing

Media	Test Number	Test Name	Use
Qualitative
ThinPrep	2007893^a	Human Papillomavirus (HPV), High Risk by Transcription-Mediated Amplification (TMA), ThinPrep	FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) in women ≥30 years Follow-up test for abnormal cytology results in women ≥21 years Detects E6/E7 viral messenger RNA of high-risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 associated with cervical cancer and its precursor lesions
ThinPrep	2011947^a	Human Papillomavirus (HPV), High Risk by PCR, ThinPrep	FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) for women ≥30 years Follow-up test for abnormal cytology results in women ≥21 years 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)
SurePath	2011942^a	Human Papillomavirus (HPV), High Risk by PCR, SurePath	FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) for women ≥30 years Follow-up test for abnormal cytology results in women ≥21 years. Test amplifies DNA of 14 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) associated with cervical cancer and its precursor lesions
Genotyping
ThinPrep	2007894^b	Human Papillomavirus (HPV) Genotypes 16 and 18/45 by Transcription-Mediated Amplification (TMA), ThinPrep	FDA-approved test for triaging women ≥30 years with negative cervical cytology (NILM Pap smear) and positive HPV test Detects E6/E7 viral messenger RNA of high-risk HPV types 16, 18, and 45 only
High Risk and Genotyping Multiplexed Assay
ThinPrep	2007890^b	Human Papillomavirus (HPV), High Risk by Transcription-Mediated Amplification (TMA) with Reflex to HPV Genotypes 16 and 18/45 by TMA, ThinPrep	FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) in women ≥30 years; genotyping performed for triaging women to colposcopy who are cytology-negative (NILM) and HPV-positive Reflex pattern – if HPV, high risk is positive, then HPV genotypes 16, 18/45 will be added
SurePath	2011933^b	Human Papillomavirus (HPV), High Risk with 16 and 18 Genotype by PCR, SurePath	FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) for women ≥30 years Follow-up test for abnormal cytology results in women ≥21 years. 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
^aQualitative testing – determines if high-risk genotypes are present but does not identify individual genotypes ^bGenotype testing – determines presence of high-risk genotype (16 or 18) For collection information, refer to ARUP Laboratories’ Test Directory (available by clicking on each test number above)

Co-testing

Media	Test Number	Test Name	Use
ThinPrep	2000136	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)	FDA-approved test for 5-year interval testing (co-testing) in women ≥30 years
SurePath	2000133	Cytology, SurePath Liquid-Based Pap Test and Human Papillomavirus (HPV), High Risk by PCR, SurePath (for routine co-testing in women over 30)	FDA-approved test for routine co-testing in women >30 Reflex pattern – if SurePath liquid-based Pap test is interpreted as satisfactory, then HPV, high risk by PCR (SurePath) will be added; unsatisfactory SurePath liquid-based Pap test specimens will not be tested for HPV
For collection information, refer to ARUP Laboratories’ Test Directory (available by clicking on each test number above)

In situ hybridization

Media	Test Number	Test Name	Use
In situ hybridization	2002899	Human Papillomavirus (HPV), High Risk by in situ Hybridization, Paraffin	Preferred in situ hybridization test to detect high-risk HPV subtypes (16, 18) to determine potential cancer risk
In situ hybridization	2002896	Human Papillomavirus (HPV) Low Risk by in situ Hybridization, Paraffin	Detects low-risk HPV subtypes 6 and 11; preferred test is HPV high-risk in situ hybridization if determining potential cancer risk
For collection information, refer to ARUP Laboratories’ Test Directory (available by clicking on each test number above)

Cytology only

Media	Test Number	Test Name	Use
ThinPrep	2000137	Cytology, ThinPrep Pap Test	May be used for routine 3-year interval cervical cancer screening in all women ≥21 years For 5-year interval testing (co-testing) in women 30-65 years, order with hrHPV PCR, ThinPrep or hrHPV by TMA, ThinPrep
SurePath	2000134	Cytology, SurePath Liquid-Based Pap Test	May be used for routine 3-year interval cervical cancer screening in all women For 5-year interval testing (co-testing) in women 30-65 years, order with hrHPV by PCR, SurePath or HPV 16 and 18 genotype PCR, SurePath
For collection information, refer to ARUP Laboratories’ Test Directory (available by clicking on each test number above)

Cytology with reflex to hrHPV testing

Media	Test Number	Test Name	Use
ThinPrep	2000138	Cytology, ThinPrep Pap Test with Reflex to Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification (TMA)	FDA-approved test for routine cervical cancer screening in women 21-<25 years Optional to use for 3-year cervical cancer screening intervals in women 25-65 years Preferred co-testing panel is cytology ThinPrep Pap test and hrHPV E6/E7 mRNA by TMA Reflex pattern – if ThinPrep Pap test is interpreted as atypical squamous cells of undetermined significance (ASC-US), then hrHPV, E6/E7 mRNA by transcription-mediated amplification (TMA) will be added
SurePath	2000135	Cytology, SurePath Liquid-Based Pap Test with Reflex to Human Papillomavirus (HPV), High Risk by PCR, SurePath	FDA-approved test for routine cervical cancer screening in women 21-<25 year Optional to use for 3-year cervical cancer screening intervals in women 25-65 years Reflex pattern – if SurePath liquid-based Pap test is interpreted as ASC-US, then hrHPV by PCR, SurePath will be added
For collection information, refer to ARUP Laboratories’ Test Directory (available by clicking on each test number above)

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

Summary of cervical cancer screening options based on age group (age groups linked to HPV screening algorithms)

Cervical Cancer Screening Options (Based on Age Group)
Age Range	Cytology	Primary HPV Testing	Co-Testing	Comments
<21	N/A	N/A	N/A	No cervical cancer screening recommended
21-<25	♦			Cytology is preferred method for this age group
25-<30	♦	♦
30-65	♦	♦	♦
>65			♦	Co-testing for these women is an option if prior screening was inadequate
Source: Saslow, ACS/ASCCP/ASCP, 2012

Women under 21 years – HPV screening recommendations and management of screen results

HPV Screening Recommendations for Women <21 Years
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 and management of screen results

HPV Screening Recommendations for Women 21-<25 Years

(Women 21-<25 years algorithm available)

Screening Method of Choice

ARUP Tests

Management of Screen Results

Cytology

(alone or with reflex)

Cytology

Cytology, ThinPrep Pap Test 2000137
Cytology, SurePath Liquid-Based Pap Test 2000134 (note: can be used only if Option 1 will be chosen for ASC-US cytology )

Cytology with reflex to HPV testing

Cytology, ThinPrep Pap Test with Reflex to Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification (TMA) 2000138
Cytology, SurePath Liquid-Based Pap Test with Reflex to Human Papillomavirus (HPV), High Risk by PCR, SurePath 2000135

HPV testing (for follow-up of ASC-US cytology)

Human Papillomavirus (HPV), High Risk by Transcription-Mediated Amplification (TMA), ThinPrep 2007893
Human Papillomavirus (HPV), High Risk by PCR, ThinPrep 2011947
Human Papillomavirus (HPV), High Risk by PCR, SurePath 2011942

Normal cytology

Repeat cytology in 3 yrs

ASC-US cytology

OPTION 1 – repeat cytology in 1 yr
OPTION 2 – HPV testing
- HPV negative – return to routine screening (choice of screening based on age; do not initiate next testing until 3 yrs from last normal or negative test)
- HPV positive – refer to ASCCP consensus guidelines (Figure 5, p. S10)

LSIL or more severe cytology

Refer to ASCCP consensus guidelines (Figure 6, p. S11)

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.

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

Women 25 to under 30 years – HPV screening recommendations and management of screen results

HPV Screening Recommendations for Women 25-<30 Years

(Women 25-<30 years algorithm available)

Screening Method of Choice

ARUP Tests

Management of Screen Results

OPTION 1

Primary hrHPV testing with genotyping

Primary hrHPV testing

Human Papillomavirus (HPV), High Risk with 16 and 18 Genotype by PCR, ThinPrep 2011940 (note: client should retain aliquot for cytology testing in case of hrHPV positivity)

Cytology for follow-up of hrHPV positive types other than 16/18

Cytology, ThinPrep Pap Test 2000137

HPV type 16/18 positive

Colposcopy

Any of other 12 hrHPV positive

Cytology
- ≥ASC-US – colposcopy
- NILM – repeat cytology in 1 yr

HPV negative

Return to routine screening
Choice of screening based on age; do not initiate testing until 3 yrs from last normal or negative test

OPTION 2

Cytology (alone or with reflex)

Cytology

Cytology, ThinPrep Pap Test 2000137
Cytology, SurePath Liquid-Based Pap Test 2000134

Cytology with reflex to HPV testing

Cytology, ThinPrep Pap Test with Reflex to Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification (TMA) 2000138
Cytology, SurePath Liquid-Based Pap Test with Reflex to Human Papillomavirus (HPV), High Risk by PCR, SurePath 2000135

HPV testing (for follow-up of ASC-US cytology)

Human Papillomavirus (HPV), High Risk by Transcription-Mediated Amplification (TMA), ThinPrep 2007893
Human Papillomavirus (HPV), High Risk by PCR, ThinPrep 2011947

Normal cytology

Repeat cytology in 3 yrs

ASC-US cytology

OPTION 1 – repeat cytology in 1 yr
OPTION 2 – HPV testing
- HPV negative – return to routine screening
  - Choice of screening based on age; do not initiate next testing until 3 yrs from last normal or negative test
- HPV positive – refer to ASCCP consensus guidelines (Figure 5, p. S10)

LSIL or more severe cytology

Refer to ASCCP consensus guidelines (Figure 6, p. S11)

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

Women 30 to 65 years – HPV screening recommendations and management of screen results

HPV Screening Recommendations for Women 30-65 Years

(Women 30-65 years algorithm available)

Screening Method of Choice

ARUP Tests

Management of Screen Results

OPTION 1

Primary hrHPV testing with genotyping

Primary hrHPV testing

Human Papillomavirus (HPV), High Risk with 16 and 18 Genotype by PCR, ThinPrep 2011940 (note: client should retain aliquot for cytology testing in case of hrHPV positivity)

Cytology for follow-up of hrHPV positive types other than 16/18

Cytology, ThinPrep Pap Test 2000137

HPV type 16/18 positive

Colposcopy

Any of other 12 hrHPV positive

Cytology
- ≥ASC-US – colposcopy
- NILM – repeat cytology in 1 yr

HPV negative

Return to routine screening
Choice of screening based on age; do not initiate testing until 3 yrs from last normal or negative test

OPTION 2

Co-testing (hrHPV and cytology)

Order co-testing bundled or cytology and HPV NAAT testing concurrently

Bundled co-testing

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

Co-testing (order the following concurrently)

Cytology, ThinPrep Pap Test 2000137 AND Human Papillomavirus (HPV), High Risk by TMA, ThinPrep 2007893 OR HPV, High Risk by PCR, ThinPrep 2011947

Cytology, SurePath Liquid-Based Pap Test 2000134 AND Human Papillomavirus (HPV), High Risk by PCR, SurePath 2011942

Primary hrHPV testing (to follow-up normal cytology and HPV positive result)

Human Papillomavirus (HPV), High Risk with 16 and 18 Genotype by PCR, ThinPrep 2011940 (note: client should retain aliquot for cytology testing in case of hrHPV positivity)

Normal cytology and HPV negative

Repeat screening of choice at 5 yrs (cytology alone every 3 yrs is acceptable)

ASC-US cytology and HPV negative

Repeat co-testing at 3 yrs

Normal cytology and HPV positive

OPTION 1 – repeat co-testing in 1 yr
- If HPV negative – repeat co-testing in 3 yrs
- If HPV positive – refer to ASCCP consensus guidelines (Figure 3, p. S8)
OPTION 2 – primary hrHPV testing
- HPV type 16/18 positive – colposcopy
- HPV type 16/18 negative – repeat co-testing in 1 yr

ASC-US cytology and HPV positive

Refer to ASCCP consensus guidelines (Figure 4, p. S9

LSIL or more severe cytology

Refer to ASCCP consensus guidelines (Figure 6, p. S11)

OPTION 3

Cytology

(alone or with reflex)

Cytology

Cytology, ThinPrep Pap Test 2000137
Cytology, SurePath Liquid-Based Pap Test 2000134 (note: can be used only if Option 1 will be chosen for ASC-US cytology)

Cytology with reflex to HPV testing

Cytology, ThinPrep Pap Test with Reflex to Human Papillomavirus (HPV), High Risk, E6/E7 mRNA by Transcription-Mediated Amplification (TMA) 2000138
Cytology, SurePath Liquid-Based Pap Test with Reflex to Human Papillomavirus (HPV), High Risk by PCR, SurePath 2000135

HPV testing (for follow-up of ASC-US cytology)

Human Papillomavirus (HPV), High Risk by Transcription-Mediated Amplification (TMA), ThinPrep 2007893
Human Papillomavirus (HPV), High Risk by PCR, ThinPrep 2011947

Normal cytology

Repeat cytology in 3 yrs

ASC-US cytology

OPTION 1 – repeat cytology in 1 yr
OPTION 2 – HPV testing
- HPV negative – return to routine screening (choice of screening based on age; do not initiate next testing until 3 yrs from last normal or negative test)
- HPV positive – refer to ASCCP consensus guidelines (Figure 5, p. S10)

LSIL or more severe cytology

Refer to ASCCP consensus guidelines (Figure 6, p. S11)

Women over 65 years – HPV screening recommendations and management of screen results

HPV Screening Recommendations for Women >65 Years (Women >65 years algorithm available)
Screening Method of Choice	ARUP Tests	Management of Screen Results
Prior screening was adequate and negative^a	N/A	No further screening
Prior screening inadequate Co-testing (hrHPV and cytology) Order co-testing bundled or cytology and HPV NAAT testing concurrently	Bundled co-testing 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 Co-testing (order the following concurrently) Cytology, ThinPrep Pap Test 2000137 AND Human Papillomavirus (HPV), High Risk by TMA, ThinPrep 2007893 OR Human Papillomavirus (HPV), High Risk by PCR, ThinPrep 2011947 OR Cytology, SurePath Liquid-Based Pap Test 2000134 AND Human Papillomavirus (HPV), High Risk by PCR, SurePath 2011942 Primary hrHPV testing (to follow-up normal cytology and HPV positive result) Human Papillomavirus (HPV), High Risk with 16 and 18 Genotype by PCR, ThinPrep 2011940 (note: client should retain aliquot for cytology testing in case of hrHPV positivity)	Normal cytology and HPV negative Screen as per 30-65 yrs until adequate screening definition fulfilled ASC-US cytology and HPV negative Recommend additional surveillance with repeat screening in 1 yr Preferred – co-testing Acceptable – cytology OR HPV PCR Normal cytology and HPV positive OPTION 1 – repeat co-testing in 1 yr If HPV negative – repeat co-testing in 3 yrs If HPV positive – refer to ASCCP consensus guidelines (Figure 3, p. S8) OPTION 2 – primary hrHPV testing HPV type 16/18 positive – colposcopy HPV negative – repeat co-testing in 1 yr ASC-US cytology and HPV positive Refer to ASCCP consensus guidelines (Figure 4, p. S9) LSIL or more severe cytology Refer to ASCCP consensus guidelines (Figure 6, p. S11)
History of ≥CIN2+	Refer to above	Use screening based on schedule for 30-65 yrs Screen for at least 20 yrs after CIN2+ test
^aAdequate 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 ASC-US = atypical squamous cells of undetermined significance; hrHPV = high-risk HPV testing; NILM = negative for intraepithelial lesion or malignancy

Post hysterectomy – HPV screening recommendations and management of screen results

Screening method of choice	Management of screen results
No history of CIN2+	No screening

Post HPV vaccination – HPV screening recommendations and management of screen results

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 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

ARUP Laboratories' HPV testing options for males

ARUP HPV Testing Options for Males
Test Number	ARUP Test
2011947	Human Papillomavirus (HPV), High Risk by PCR, ThinPrep
2011942	Human Papillomavirus (HPV), High Risk by PCR, SurePath
Refer to ARUP Laboratories’ Test Directory for collection information (available by clicking on each test number above)

HPV Testing in Head and Neck Cancer

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

Indications for Testing

Refer to Key Points section
Disease management guidelines and algorithms available from the American Society for Colposcopy and Cervical Pathology (ASCCP, 2012)

Laboratory Testing

Refer to Key Points section

Human Papillomavirus Screening Recommendations Women 21 to under 25 Years of Age Algorithm

Read more about Human Papillomavirus Screening Recommendations Women 21 to under 25 Years of Age Algorithm

Human Papillomavirus Screening Recommendations Women 25 to under 30 Years of Age Algorithm

Read more about Human Papillomavirus Screening Recommendations Women 25 to under 30 Years of Age Algorithm

Human Papillomavirus Screening Recommendations Women 30-65 Years of Age Algorithm

Read more about Human Papillomavirus Screening Recommendations Women 30-65 Years of Age Algorithm

Human Papillomavirus Screening Recommendations Women older than 65 Years of Age Algorithm

Read more about Human Papillomavirus Screening Recommendations Women older than 65 Years of Age Algorithm

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
- Also a risk factor for anal, penile, and oropharyngeal 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

Recommended Use

Media – ThinPrep

FDA-approved platform for primary HPV screening in women ≥25 years

FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) in women ≥30 years

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

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

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

Recommended Use

Media – ThinPrep

FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) in women ≥30 years; genotyping performed for triaging women to colposcopy who are cytology negative (NILM) and HPV positive

Reflex pattern – if HPV, high risk, is positive, then HPV genotypes 16, 18/45 will be added

Follow-up

Refer to Key Points section

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

Recommended Use

Media – ThinPrep

FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) in women ≥30 years

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

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

Follow-up

Refer to Key Points section

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

Recommended Use

Media – ThinPrep

FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) for women ≥30 years

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

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)

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

Recommended Use

Media – ThinPrep

FDA-approved test for triaging women ≥30 years with negative cervical cytology (NILM Pap smear) and positive HPV test

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

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

Recommended Use

Media – SurePath

FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) for women ≥30 years

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

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

Follow-up

Refer to Key Points section

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

Recommended Use

Media – SurePath

FDA-approved test for routine cervical cancer screening in combination with cervical cytology (Pap smear) for women ≥30 years

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

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

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

Recommended Use

Media – ThinPrep

Preferred FDA-approved test for 5-year interval testing (co-testing) in women ≥30 years

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

Recommended Use

Media – SurePath

FDA-approved test for routine co-testing in women >30

Reflex pattern – if SurePath liquid-based Pap test is interpreted as satisfactory, then HPV, high risk by PCR (SurePath) will be added; unsatisfactory SurePath liquid-based Pap test specimens will not be tested for HPV

Limitations

Test has an inherent false-negative rate

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

Recommended Use

Preferred in situ hybridization test to detect high-risk HPV subtypes (16, 18) in formalin-fixed, paraffin-embedded tissue to determine potential cancer risk

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

Recommended Use

Detects low-risk HPV subtypes 6 and 11

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

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

Recommended Use

Media – SurePath

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

For 5-year interval testing (co-testing) in women 30-65 years, order with hrHPV PCR, SurePath or HPV 16 and 18 genotype PCR, SurePath

Test does not include HPV testing

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

Recommended Use

Media – ThinPrep

May be used for routine 3-year interval cervical cancer screening in all women ≥21 years

For 5-year interval testing (co-testing) in women 30-65 years, order with hrHPV PCR, ThinPrep or hrHPV by TMA, ThinPrep

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

Recommended Use

Media – ThinPrep

Preferred FDA-approved test for routine cervical cancer screening in women 21-<25 years

Optional to use for 3-year cervical cancer screening intervals in women 25-65 years

Preferred co-testing panel is cytology ThinPrep Pap test and hrHPV by TMA

Reflex pattern – if ThinPrep Pap test is interpreted as atypical squamous cells of undetermined significance (ASC-US), then hrHPV, E6/E7 mRNA by transcription-mediated amplification (TMA) will be added

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

Recommended Use

FDA-approved test for routine cervical cancer screening in women 21-<25 years

Reflex pattern – if SurePath liquid-based Pap test is interpreted as ASC-US, then hrHPV PCR, SurePath will be added

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

Chadwick, Barbara E., MD, Medical Director, Cytology, and Staff Pathologist, Surgical Pathology at ARUP Laboratories; Assistant Professor of Anatomic Pathology, University of Utah

Schlaberg, Robert, MD, MPH, Medical Director, Microbial Amplified Detection, Virology, and Fecal Chemistry; and Assistant Medical Director, Virology and Molecular Infectious Disease at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Cervical Cancer

Head and Neck Cancer

Sexually Transmitted Infections

Treponema pallidum - Syphilis

Tumor Markers

HPV Testing for Cervical Cancer Screening -- Robert Schlaberg, MD, MPH (51 min)

Molecular Testing and Cytopathology: Downsizing Precision Medicine but not Precision - Georgios Deftereos, MD, FCAP, FASCP (FREE CME credit) (50 min)

Spotlight on Test Utilization: Clinical Performance Comparison of FDA-Cleared HPV Tests - Robert Schlaberg, MD, MPH (5 min)

Spotlight on Test Utilization: HPV Testing for Cervical Cancer Screening -- Robert Schlaberg, MD, MPH (4 min)

Update on HPV Testing - Robert Schlaberg, MD, Dr Med, MPH (FREE CME credit) (42 min)

Content Reviewed:

July 2017

Last Update: September 2017


	Schlaberg R. Human Papillomavirus - HPV. ARUP Consult^©. Retrieved September 15, 2017, from: https://arupconsult.com/content/human-papillomavirus

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Human Papillomavirus - HPV

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Human Papillomavirus Testing in Women

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ARUP Laboratories’ Cervical Cancer and HPV Screening Tests

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HPV Testing in Head and Neck Cancer

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Human Papillomavirus Screening Recommendations Women 21 to under 25 Years of Age Algorithm

Human Papillomavirus Screening Recommendations Women 25 to under 30 Years of Age Algorithm

Human Papillomavirus Screening Recommendations Women 30-65 Years of Age Algorithm

Human Papillomavirus Screening Recommendations Women older than 65 Years of Age Algorithm

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References from the ARUP Institute for Clinical and Experimental Pathology®

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