HPV and Cervical Cancer Screening Medical Guidelines

Wright, T. et al. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. American Journal of Obstetrics & Gynecology 2007; 197(4):346-355.

Developed by 146 experts representing 29 organizations, these updated guidelines included several recommendations governing cervical cancer screening:

• HPV testing is the preferred method of follow-up evaluation for women age 20-30 with ASC-US cytology. If testing shows they do not have HPV, a repeat Pap is recommended in 12 months. If HPV is present, colposcopy is the next step.

  For girls under 20: The guidelines state that HPV testing is not warranted in adolescents for any reason. Young girls with ASC-US cytology should get a repeat Pap in 12 months. At that time, only those with cytology of HSIL or greater should be referred to colposcopy. At the 24-month follow-up, girls with cytology results of ASC-US or greater should be referred to colposcopy.

• Routine HPV testing, along with a Pap, is beneficial for screening women 30 and older.

  Depending on the test results, the next steps outlined below are recommended:

  	Normal Pap	ASC-US Pap	Abnormal Pap
  No HPV	Repeat screening with both the HPV and Pap tests every three years.	Repeat Pap in 12 months	Colposcopy
  HPV	Repeat both the HPV and Pap tests in 12 months. If either test is abnormal at that time, colposcopy is warranted.	Colposcopy	Colposcopy

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Centers for Disease Control and Prevention, "Human Papillomavirus: HPV Information for Clinicians," www.cdc.gov/STD/Hpv/hpv-clinicians-brochure.htm. April 2007.

In April 2007, the CDC published a brochure titled "HPV Information for Clinicians." It offers these guidelines:

• Girls and young women: The Advisory Committee on Immunization Practices recommends that the HPV vaccine be given to girls and young women age 11-26, and stated that it can be administered to girls as young as 9.

  Ideally, the vaccine should be given before a girl becomes sexually active, and thus exposed to HPV. If given afterwards, the vaccine will only protect her against the HPV type(s) to which she has not yet been exposed. In addition, it is not yet known whether a "booster" shot is needed later in life.

  In any case, no matter if or when vaccination occurs, screening for cervical cancer risk is still needed, since the protection offered by the HPV vaccine is incomplete.

• Women of all ages: Regular Pap testing should begin three years after a young woman has sexual intercourse for the first time, or at the age of 21 – whichever comes first. The CDC recognizes that several leading medical organizations – including the American College of Obstetricians and Gynecologists, the American Cancer Society, and the American Society for Colposcopy and Cervical Pathology – endorse the use of HPV testing along with the Pap for women age 30 and over.

ACOG Practice Bulletin No. 66, "Management of Abnormal Cervical Cytology and Histolog: Clinical Management Guidelines for Obstetrician-Gynecologists." September 2005.

In September 2005, ACOG issued a practice bulletin titled, "Management of Abnormal Cervical Cytology and Histology." In addition to providing a background on cytologic and histologic findings and interpretation, the document outlines how HPV DNA testing can be used to help manage patients with varying levels of cervical abnormalities. An ACOG practice bulletin on HPV issued in April 2005 reported that HPV testing is "more sensitive than cervical cytology" for detection of pre-cancerous cells and cervical cancer. It further stated that combining HPV testing with cytology has "a negative predictive value for CIN 2 and CIN 3 of 99 to 100 percent," and offered that "because HPV DNA testing is more sensitive than cervical cytology, women with negative concurrent test results can be reassured that their risk of unidentified CIN 2 and CIN 3 or cervical cancer is approximately 1 in 1,000."

Addressing the impact of test results on patient management, ACOG recognized the interim patient management guidelines published in 2004 (see below) which recommended that women older than 30 years who have high-risk HPV but negative cytology "should have both tests repeated in 6-12 months", also noting that women with persistent HPV on repeat testing "should undergo colposcopy regardless of the cytology result."

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ACOG Practice Bulletin No. 61, "Human Papillomavirus. Clinical Management Guidelines for Obstetrician-Gynecologists." April 2005. 

In April 2005, the American College of Obstetricians and Gynecologists (ACOG) published a practice bulletin recognizing HPV testing as "more sensitive than cervical cytology" for detection of pre-cancerous cells (CIN 2/3) and cervical cancer. The bulletin concluded, as a "Level A" recommendation:

• Because HPV DNA testing is more sensitive than cervical cytology in detecting CIN 2 and CIN 3, women with negative concurrent test results can be reassured that their risk of unidentified CIN 2 and CIN 3 or cervical cancer is approximately 1 in 1,000."

• "Studies using combined HPV testing with cervical cytology have reported a negative predictive value for CIN 2 and CIN 3 of 99 to 100 percent."

As support for these conclusions, the practice bulletin cited a study in which 100 percent of cancerous lesions were detected using HPV DNA testing, compared to 58 percent with conventional cytology and 84 percent with liquid-based Paps. "Even newer liquid-based cytology techniques may miss 15-35 percent of cervical intraepithelial neoplasia (CIN) 3 or cancer. This carries important medical implications and has stimulated substantial interest in the development of more sensitive screening tools," reported the ACOG bulletin.

As "Level C" guidance, the bulletin touched on incorporation of test results into patient management, recognizing the 2004 NIH/ASCCP/ACS interim guidance and reiterating recommendations that, "women older than 30 years with a negative cytology result who have high-risk HPV DNA-positive test results should have both tests repeated in 6-12 months. Those with persistent HPV (on repeat testing) should undergo colposcopy regardless of the cytology result."

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Wright, T. et al. Interim Guidance for the Use of HPV DNA Testing as an Adjunct to Cervical Cytology for Screening. Obstet and Gynecol 2004; 103:304–9.

Published in 2004 in Obstetrics and Gynecology (also known as "The Green Journal"), this guidance was developed during a workshop supported by the NIH, ASCCP and ACS. For the first time, it provided guidance to healthcare professionals for managing women with various Pap and HPV test results. The guidance noted that women with negative/normal cytology who are positive for high-risk HPV are at a relatively low risk of having high-grade cervical neoplasia, and thus recommended against performing colposcopy unless re-testing in 6 to 12 months showed persistent infection.. [Note that as of October 2007, the ASCCP now recommends re-testing in 12 months.] 

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ARHP Clinical Proceedings, "Advances in Cervical Cancer Prevention." September 2003.

In September 2003, ARHP published a document called Clinical Proceedings: Advances in Cervical Cancer Prevention, which included use of high-risk HPV testing in conjunction with cytology in women age 30 and older. (Since then, the ARHP has published a special issue of its magazine Health & Sexuality devoted to HPV.)

ACOG Practice Bulletin No. 45, "Cervical Cytology Screening." Clinical Management Guidelines for Obstetrician-Gynecologists." August 2003.

The U.S. FDA approved the digene HPV Test^* (first introduced as the DNAwithPap® Test) for primary adjunctive screening together with a Pap in women 30 and over. In July 2003, ACOG issued a practice bulletin for cervical cytology screening. It included guidance for the combined use of a Pap and the FDA-approved high-risk HPV test for women age 30 and older:

For women age 30 and older, there are two acceptable screening options:

• Testing using cervical cytology alone: If a woman has negative results on three consecutive annual Paps (and does not have any other "disqualifying" characteristics), then she should be re-screened with cytology alone every two to three years.

• Combined use of cytology and HPV DNA screening: Once women test negative on both tests they should be re-screened no more frequently than every three years. Note that since the digene HPV Test* was not yet approved for primary adjunctive screening at the time these guidelines were written, ACOG stated that this recommendation was based on "limited and inconsistent scientific evidence."

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Saslow D, et al. American Cancer Society Guidelines for the Early Detection of Cervical Neoplasia and Cancer. CA Cancer J Clin 2002; 52:342–362.

Published in November 2002, the American Cancer Society guidelines recommended that healthcare professionals consider combining cytology with testing for high-risk HPV DNA for cervical cancer screening in women age 30 and older, contingent upon FDA approval (which followed in 2003).

The ACS guidelines stated that "HPV DNA testing has greater sensitivity than cytology for detecting clinically relevant lesions," and that the "high negative predictive value resulting from concomitant screening with cytology and HPV DNA testing could safely permit increasing screening intervals, thus lowering costs."

The guidelines also stated: "It would be reasonable to consider that for women aged 30 and over, as an alternative to cervical cytology testing alone, cervical screening may be performed every three years using conventional or liquid-based cytology combined with a test for DNA from high-risk HPV types."

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Wright T.C., et al. 2001 Consensus Guidelines for the Management of Women with Cervical Cytological Abnormalities. JAMA 2002;287: 2120–29.

In 2001, the American Society for Colposcopy and Cervical Pathology (ASCCP) issued the first evidence-based, national practice guidelines for managing patients with abnormal Pap results. This organization's 2001 consensus guidelines were developed with input from 29 leading medical organizations, including the National Cancer Institute, the Centers for Disease Control and Prevention, and the American Cancer Society. They followed by about one year the FDA’s approval of digene's HPV test, then known as the Hybrid Capture® 2 (hc2) High-Risk HPV DNA Test®, for triage of ASC-US Pap results.

The consensus guidelines stated that when managing women with ASC-US Pap results, HPV testing is the "preferred approach" when it can be performed directly from a liquid–based Pap sample ("reflex" HPV testing) or when a separate specimen can be collected for HPV testing during the initial office visit.