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Managing HPV: A New Era in Patient Care

(Published June 2009)

Management of Abnormal Cervical Cancer Screening Results

The American Society for Colposcopy and Cervical Pathology (ASCCP) published updated national guidelines for the management of abnormal results from cervical cancer screening. These guidelines differ from those published in 2001 in several important ways, including the management of abnormal results in postmenopausal women and other specific populations. This chapter will discuss the current guidelines for most populations; a subsequent chapter will cover management of cervical cancer screening results in adolescents. Algorithms based on these guidelines are available at www.asccp.org/consensus.shtml. Table 3 provides a review of the clinical significance of cytology screening results.

Table 3: Clinical Significance of Cervical Cytology Screening Results1-5
Cytology Screening Results Clinical Significance* Comments
Atypical squamous cells of undetermined significance (ASCUS)

7% to 15% have CIN-2,3; women with a cytological result of ASCUS require follow-up

Most common cytological abnormality in the United States; almost half of all cases of CIN-2,3 are diagnosed in women with ASCUS

Atypical squamous cells cannot exclude HSIL (ASC-H)

26% to 68% have CIN-2,3; includes both HSIL and mimics

Relatively uncommon; relatively high frequency of CIN-2,3 or higher in this population (therefore, all women with ASC-H should undergo colposcopy)

Low-grade squamous intraepithelial lesion (LSIL)

12% to 25% have CIN-2,3; usually represents self-limited HPV infection

Relatively common; found more commonly in liquid-based than conventional Pap specimens
High-grade intraepithelial lesion (HSIL) Approximately 2% have invasive cancer; more often associated with persistent infection and progression than LSIL

Relatively uncommon; detecting CIN-2,3 has emerged as the central purpose of screening

Atypical glandular cells (AGC) 3% to 17% have invasive cancer — including adenocarcinomas of the cervix, endometrium, ovary, and fallopian tube Relatively uncommon; more common in women >40 years old

Management of Atypical Squamous Cells of Undetermined Significance

National guidelines for management of ASCUS in premenopausal women remain unchanged from previous guidelines. ASCCP recommends three options for initial management in premenopausal women:4

  • Human papillomavirus (HPV) DNA testing or
  • Repeat cytology at six and 12 months or
  • Colposcopy

Of these, HPV DNA testing is the preferred option if liquid-based cytology or co-collection is used. For follow-up management of ASCUS in women who did not undergo colposcopy initially, the guidelines recommend that:4

  • If HPV reflex testing was used initially and the results were negative, the Pap test should be repeated in 12 months. If HPV test results were positive, colposcopy should be performed.
  • If repeat cytology was used initially and Pap tests are negative at both six and 12 months, the patient can return to routine screening. If either Pap test shows a result of ASC or greater, the woman should undergo colposcopy.

For follow-up management of ASCUS in women who underwent colposcopy initially and had no CIN identified, the guidelines recommend:

  • HPV DNA testing at 12 months (it is recommended that HPV DNA testing not be performed at intervals less than 12 months) or
  • Repeat cytological testing at six and 12 months

If CIN is identified in women who underwent initial colposcopy for ASCUS management, follow-up should be directed by guidelines for CIN management, which will be discussed later in this chapter.

Postmenopausal women and immunosuppressed women

In contrast with the 2001 consensus guidelines, the updated guidelines recommend that ASCUS in postmenopausal women and immunosuppressed women should be managed in the same manner as for the general population.4,6

Atypical Squamous Cells, Cannot Exclude HSIL

The ASCCP guidelines recommend colposcopy for all women with ASC-H, based on the fact that a number of studies have reported high rates of CIN-2,3 in these women.4,6

Low-Grade Squamous Intraepithelial Lesion

Table 4: ASCCP Recommended Initial Management of LSIL4,5
Results of Initial Testing Recommended Follow-up
Colposcopy was unsatisfactory Endocervical sampling

No lesion visible on colposcopy

Endocervical sampling

Biopsy showed CIN-2,3

See ASCCP guidelines for CIN management (discussed later in this chapter)

Biopsy showed no CIN-2,3

Repeat Pap test at 6 and 12 months or HPV testing at 12 months

The 2006 ASCCP guidelines recommend colposcopy for women with LSIL but with special provisions and other options for postmenopausal women and pregnant women. Recommendations for initial and follow-up management are shown in Tables 4 and 5.

The 2006 ASCCP guidelines differ from those published in 2001 in recommended management of LSIL for postmenopausal women and pregnant women.4

Postmenopausal women

The new guidelines recommend three options for LSIL management in postmenopausal women:4

  • Reflex HPV DNA testing or
  • Colposcopy or
  • Repeat Pap test at six and 12 months
    Table 5: ASCCP Recommended Follow-up Management of LSIL4
    Results of Testing After Biopsy Recommended Follow-up
    Pap test result is normal x2 (at 6 and 12 months) or HPV test result (at 12 months) is negative Return to routine screening
    Pap test result is ASC or greater or HPV test result is positive Repeat colposcopy

Pregnant women

The 2006 guidelines consider colposcopy to be preferred for nonadolescent pregnant women.4 The guidelines note that endocervical curettage is unacceptable for pregnant women and that deferring colposcopy until six weeks postpartum is an acceptable option. In addition, postpartum follow-up is recommended for pregnant women with no suspected CIN-2,3 or cancer at the initial colposcopy. The guidelines state that additional colposcopic and cytological examinations during pregnancy are unacceptable management options for these women.4

Management of Atypical Glandular Cells

The 2006 ASCCP guidelines recommend colposcopy with endocervical sampling (i.e., endocervical curettage) for all women with AGC.4 Women age 35 or older should have endometrial sampling, colposcopy, and endocervical sampling. In addition, the guidelines recommend endometrial sampling for women of any age who have abnormal bleeding suggestive of a risk for neoplastic endometrial lesions. The ASCCP guidelines state that patients with AGC should have HPV testing at the time of colposcopy.4 Management after the colposcopy depends on the colposcopy, biopsy, endocervical sampling, and HPV test results.

After colposcopy, the ASCCP guidelines recommend that “atypical endocervical, endometrial, or glandular cells (NOS)” should be managed based on results of biopsies and endocervical sample:4

  • If the biopsies and endocervical samples are negative for neoplasia and the HPV status is unknown, the Pap test should be repeated every six months for up to four times, with a referral to colposcopy for a result of ASC or greater.
  • If the HPV status is known to be negative, the Pap test and HPV DNA testing should be repeated in 12 months.
  • If the HPV status is known to be positive, the Pap test and HPV DNA testing should be repeated in six months.

Patients with known HPV status should be referred for colposcopy if the repeat HPV DNA test result is positive or if cytology shows a result of ASCUS or greater.4

Management of High-Grade Squamous Intraepithelial Lesion

ASCCP guidelines include two management options for women with HSIL (excluding adolescents and pregnant women):4

  • Colposcopic examination with endocervical assessment or
  • Immediate loop electrosurgical excision (“see and treat”)

If colposcopic examination with endocervical assessment is selected, the colposcopy is satisfactory, and the biopsy shows CIN-2,3, either excision or ablation of the lesion is recommended. Alternatively, if the biopsy does not show CIN-2,3, the guidelines recommend one of three treatment options:4

  • Excisional procedure or
  • Review of all findings with management based on revised findings or
  • Observation with Pap test and colposcopy every six months for one year

If the latter is selected and HSIL persists, an excisional procedure is recommended. Similarly, an excisional procedure is recommended if the colposcopy is deemed unsatisfactory.

Pregnant women

ASCCP guidelines recommend colposcopy for pregnant women with HSIL.4 The guidelines warn that endocervical curettage is unacceptable for all pregnant women.

Management of Cervical Intraepithelial Neoplasia Grade 1

ASCCP guidelines for the management of CIN-1 are dependent on the initial cervical cytology finding:6

  • If the initial Pap test result showed ASC or LSIL, guidelines recommend repeat cytology at six and 12 months or HPV DNA testing at 12 months.
  • If the initial Pap test result showed HSIL, guidelines recommend follow-up according to the HSIL management guidelines.

The guidelines note that after 24 months of follow-up, treatment of the lesion is acceptable.

The guidelines warn against routine use of excisional procedures for CIN-1.

Management of Cervical Intraepithelial Neoplasia Grades 2,3

ASCCP guidelines state that either excision or ablation is an acceptable option for the initial management of CIN-2,3, except in pregnant women and adolescents, if the colposcopy was deemed satisfactory.6 Recommended follow-up options after initial treatment include Pap testing alone or a combination of Pap testing and colposcopy at six-month intervals.

Pregnant women

If there is no evidence of invasive disease and the pregnancy is not advanced, additional colposcopy and Pap tests are acceptable (at intervals no more frequent that every 12 weeks).6 Biopsy should be repeated only if the lesion worsens or if Pap testing suggests invasive cancer. Deferring reevaluation until six or more weeks postpartum is an acceptable option.

Follow-up After Treatment of Cervical Intraepithelial Neoplasia

Follow-up is critical for women treated for CIN, because treatment failures occur and because these women remain at higher risk for invasive cervical cancer than the general population for at least 20 years.6 Although recommended follow-up has not yet been evaluated by randomized clinical trial, a reasonable option is HPV testing six months after treatment, with further management dependent on the results. Women who have negative HPV test results can return to annual screening, whereas women with positive results should undergo colposcopy.

References:

  1. Arbyn M, Sasieni P, Meijer CJ, Clavel C, Koliopoulos G, Dillner J. Chapter 9: Clinical applications of HPV testing: a summary of meta-analyses. Vaccine. 2006;24(suppl 3):S78-89.
  2. Davey DD, Neal MH, Wilbur DC, Colgan TJ, Styer PE, Mody DR. Bethesda 2001 implementation and reporting rates: 2003 practices of participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology. Arch Pathol Lab Med. 2004;128(11):1224-9.
  3. Solomon D, Davey D, Kurman R, Moriarty A, O’Conner D, Prey M, et al. The 2001 Bethesda System: terminology for reporting cervical cytology. JAMA. 2002; 287:2114-19.
  4. Wright TC, Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D. 2006 Consensus Guidelines for the Management of Women with Abnormal Cervical Cancer Screening Tests. Am J Obstet Gynecol. 2007;197(4):346-55.
  5. Castle PE, Schiffman M, Wheeler CM, Solomon D. Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol. 2009 Jan;113(1):18-25.
  6. Wright TC, Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D. 2006 Consensus Guidelines for the Management of Women with Cervical Intraepithelial Neoplasia or Adenocarcinoma in situ. Am J Obstet Gynecol. 2007;197(4):340-5.