Human Papillomavirus (HPV) Testing - Cervical Cancer Screening

Human papillomavirus (HPV) is the most common sexually transmitted viral infection and is the etiologic agent for most cases of cervical cancer. High-risk HPV genotypes are also associated with an increased risk of developing vulvar, vaginal, anal, penile, and oropharyngeal cancer. Most cases of HPV clear within 1-2 years.  The American Cancer Society (ACS), American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) jointly recommend an age-based approach to cervical cancer screening. Testing options vary depending on the woman’s age, but include cytology, cotesting, and primary high-risk HPV (hrHPV) testing. There is no routinely recommended screening test for other HPV-related cancers.

Quick Answers for Clinicians

At what age should women begin to have screening for cervical cancer? At what age should screening end?

Cytologic abnormalities are common in women younger than 21 years, yet clinically important cervical lesions are rare. To minimize the need for subsequent follow-up by colposcopy and biopsy, initial screening should begin at 21 years.    In the United States, guideline-issuing organizations recommend screening be discontinued in women 65 years and older if they are up to date on testing and have normal results.    

How often should women be screened for cervical cancer?

Annual screening for cervical cancer is not recommended for most women. Frequent screening leads to higher rates of false-positive results with little effect on subsequent development of cervical cancer because of the length of time between cervical precancerous lesions and invasion; rather, recommended screening intervals for women are based on age and clinical history, as set forth by the joint American Cancer Society/American Society for Colposcopy and Cervical Pathology/American Society for Clinical Pathology (ACS/ASCCP/ASCP) guideline. - 

Is it appropriate to screen for cervical cancer with human papillomavirus (HPV) testing alone?

In January 2015, the Society of Gynecologic Oncology (SGO) and the American Society for Colposcopy and Cervical Pathology (ASCCP), motivated by the U.S. Food and Drug Administration’s (FDA's) approval of the Roche cobas human papillomavirus (HPV) test as a primary test for cervical cancer screening, issued interim clinical guidance suggesting that primary HPV testing can be considered as an alternative to current cytology-based cancer screening methods in women 25 years and older. The drafting of the interim guidance was informed by 11 other expert representatives from organizations such as the American Cancer Society (ACS), and the guidance was endorsed by the American College of Obstetricians and Gynecologists (ACOG) and the U.S. Preventive Services Task Force (USPSTF).    

Indications for Testing

Women 21-65 years of age should be routinely screened for cervical cancer. Recommended screening intervals and testing methods are based on age group.    There is no recommendation for routine HPV screening in males. 

Laboratory Testing

HPV Testing in Women: Cervical Cancer Screening

Screening with cervical cytology and/or testing for multiple oncogenic HPV types can lead to the detection of high-grade precancerous cervical lesions and cervical cancer.  High-risk HPV genotypes are necessary for the development of cervical cancer. HPV types 16 and 18 are the most carcinogenic genotypes and account for 55-60% and 10-15% of all cervical cancers, respectively.  Low-risk HPV types are unrelated to cervical cancer and have no clinical role in cervical cancer screening or the evaluation of women with abnormal cytology.

Conventional or liquid-based cytology, with or without reflex to hrHPV testing, is the recommended screening method in women 21-29 years of age and should be performed every 3 years.  Cotesting is defined as screening by cytology and HPV testing and is the preferred screening method in women 30 years and older. This method is more sensitive than cytology alone for detecting cervical abnormalities and has the potential to improve disease detection and lengthen screening intervals.  Recent guidance from the Society of Gynecologic Oncology (SGO) and the ASCCP and endorsed by the American College of Obstetricians and Gynecologists (ACOG) suggests that primary HPV testing can be considered as an alternative screening method to cytology for women starting at 25 years of age. 

Screening Guidelines by Population

Women 21-<25 Years of Age

In women 21-<25 years of age, screening by cytology alone every 3 years is recommended. - 

Women 21-<25 Years
Testing Method Results Follow-Up
Cytology Normal cytology Repeat cytology in 3 yrs
ASC-US cytology Repeat cytology in 1 yr (preferred) OR reflex to HPV testing
LSIL cytology Repeat cytology in 1 yr (preferred) OR reflex to HPV testing
ASC-US, atypical squamous cells of undetermined significance; LSIL, low-grade squamous intraepithelial lesion
Women 25-<30 Years of Age

Interim guidance from the SGO/ASCCP suggests that primary HPV screening can be considered as an alternative to cytology for women beginning at 25 years of age.  This method of screening should be repeated no more than every 3 years in the event of a normal result.  The U.S. Preventive Services Task Force (USPSTF) and ACOG endorse the recommendation.  

Women 25-<30 Years
Testing Method Results Follow-Up
Cytology (with or without reflex) Normal cytology Repeat cytology in 3 yrs
ASC-US cytology Repeat cytology in 1 yr OR perform HPV testing (preferred)
  • HPV negative: repeat cotesting at 3 yrs
  • HPV positive: colposcopy; refer to ASCCP algorithms 
LSIL cytology Refer to ASCCP algorithms 
Primary hrHPV testing with genotyping

(ONLY for women ≥25 years)

HPV type 16/18 positive Colposcopy
Positive for any one of the other 12 hrHPV genotypes Cytology
  • ASC-US: colposcopy
  • NILM: repeat cytology in 1 yr
HPV negative Return to routine screening
NILM, negative for intraepithelial lesion or malignancy
Women 30-65 Years of Age

Most major U.S. guidelines endorse the strategy of cytology plus testing for hrHPV types (known as cotesting) in women 30-65 years as an alternative to cytology alone. -  The rationale behind cotesting is that women with normal cytologic test results and no evidence of hrHPV constitute a particularly low-risk group for whom screening intervals may be safely lengthened to every 5 years.  HPV and cytology cotesting every 5 years is preferred, but cytology without reflex every 3 years is acceptable.

Women 30-65 Years
Testing Method Results Follow-Up
Cotesting 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 cotesting at 3 yrs
Normal cytology and HPV positive OPTION 1: repeat cotesting in 1 yr
  • HPV negative: repeat cotesting in 3 yrs
  • ASC-US or HPV positive: colposcopy

OPTION 2: HPV DNA typing

  • HPV type 16/18 positive: colposcopy
  • HPV type 16/18 negative: repeat cotesting in 1 yr
ASC-US cytology and HPV positive Colposcopy
LSIL cytology Refer to ASCCP algorithms 
Primary hrHPV testing with genotyping HPV type 16/18 positive Colposcopy
Positive for any one of the other 12 hrHPV genotypes Cytology
  • ASC-US: colposcopy
  • NILM: repeat cytology in 1 yr
HPV negative Return to routine screening
Cytology (with or without reflex) Normal cytology Repeat cytology in 3 yrs
ASC-US cytology Repeat cytology in 1 yr OR perform HPV testing (preferred)
  • HPV negative: repeat cotesting at 3 yrs
  • HPV positive: colposcopy; refer to  ASCCP algorithms 
LSIL cytology Refer to ASCCP algorithms 
Women >65 Years of Age

Women older than 65 years need not be screened following an adequate and negative screen; if previous screening was inadequate, cotesting (preferred) or cytology (acceptable) should be performed. Adequate screening is considered three consecutive negative cytology results or two consecutive negative cotesting results within the last 10 years; the most recent of either test must be within the past 5 years. Women with a history of cervical intraepithelial neoplasia grade 2 (CIN2) or a more severe diagnosis should continue routine screening for at least 20 years after the CIN2-positive test.  

Women >65 Yearsa
Testing Method Results Follow-Up
Cotesting (preferred)

(hrHPV and cytology)

Normal cytology and HPV negative Screen as per women 30-65 yrs until adequate screening definition is fulfilled
ASC-US cytology and HPV negative Perform additional surveillance with repeat screening in 1 yr (cotesting is preferred, but cytology is acceptable)
Normal cytology and HPV positive OPTION 1: repeat cotesting in 1 yr
  • HPV negative: repeat cotesting in 3 years
  • ASC-US or HPV positive: colposcopy; refer to ASCCP algorithms 

OPTION 2: HPV DNA typing

  • HPV type 16/18 positive: colposcopy
  • HPV negative or positive for any one of the other 12 hrHPV genotypes: repeat cotesting in 1 yr
ASC-US cytology and HPV positive Refer to ASCCP algorithms 
LSIL cytology Refer to ASCCP algorithms 
History of ≥CIN2 Perform screening based on schedule for women 30-65 yrs of age and screen for at least 20 yrs after CIN2-positive test
Cytology (with or without reflex) Normal cytology Screen as per women 30-65 yrs until adequate screening definition fulfilled
ASC-US cytology Refer to ASCCP algorithms 
LSIL cytology Refer to ASCCP algorithms 
aIf previous screening was adequate and negative, no further screening is needed. If previous screening was inadequate, proceed with cotesting or cytology. Adequate screening is considered 3 consecutive negative cytology results or 2 consecutive negative cotesting results within the last 10 years; the most recent of either test must be within the past 5 years.
Women Posthysterectomy

Screening for vaginal cancer should not be performed at any age in women who have undergone hysterectomy with removal of the cervix and have no history of a CIN2-positive result. 

Women Post-HPV Vaccination

Screening practices should not change after HPV vaccination; age-based screening recommendations should be followed. 

HPV Testing in Men

High-risk HPVs are known to cause cancers of the penis or anus. These cancers are uncommon, and only a subset are related to HPV. Currently, there is no HPV test recommended for men, and screening for anal cancer is not routinely recommended for men. However, some experts recommend yearly anal cancer screening by cytology ("anal Pap") for men who have sex with men (MSM) and HIV-positive men (anal cancer is more common in these populations). 

Screening tests are not available for penile cancer. 

HPV Testing in Head and Neck Cancer

Refer to the ARUP Consult Head and Neck Cancer topic for testing recommendations.

ARUP Lab Tests

Cervical Cancer Testing

HPV Testing for Cervical Cancer

FDA-approved test and platform for primary HPV screening in women ≥25 yrs

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

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

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

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

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

FDA-approved test for triaging women ≥30 yrs to colposcopy who are cytology negative (NILM) and HPV positive

Cotesting (Cytology with HPV testing) for Cervical Cancer

FDA-approved test for 5-yr interval testing (cotesting) in women 30-65 yrs

Cytology with Reflex to HPV Testing for Cervical Cancer

FDA-approved test for routine cervical cancer screening in all women ≥21 yrs

Optional to use for cervical cancer screening at 3-yr intervals in women 25-65 yrs

FDA-approved test for routine cervical cancer screening at 3-yr intervals in all women ≥21 yrs

Optional to use for cervical cancer screening at 3-yr intervals in women 25-65 yrs

Cytology Testing for Cervical Cancer

FDA-approved test for routine cervical cancer screening at 3-yr intervals in all women ≥21 yrs

For 5-yr interval testing (cotesting) in women 30-65 yrs, order with HPV testing

Medical Experts

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References

Resources from the ARUP Institute for Clinical and Experimental Pathology®