Atypical squamous cells: The case for HPV testing
New data, terminology, and guidelines are in, and human papillomavirus testing is emerging as the most efficient and cost-effective triage option.
HPV-negative postmenopausal patients. All 3 management options—immediate colposcopy, repeat cytology, and HPV DNA testing—are acceptable for postmenopausal women with ASC-US.11 However, estrogen deficiency is a common cause of ASC-US and is responsible for increasing rates of HPV-negative ASC-US in this age group despite high sensitivity of HPV testing for CIN 2 and 3.5
- Treatment with vaginal estrogen cream followed by repeat cytology approximately 1 week after completing the regimen is an option for postmenopausal women with ASC-US. This approach also may be helpful for perimenopausal women and for women of any age on progestin-only contraception who have clinical or cytologic evidence of atrophy.
- Women with ASC-US or greater on repeat cytology should be referred for colposcopy, whereas women with normal repeat cytology should have a second Pap test in 4 to 6 months. Repeating the course of vaginal estrogen prior to each Pap test may be helpful when atrophy is likely to persist. After 2 normal repeat Pap tests, the patient can return to routine screening.
Refer all immunosuppressed women for colposcopy. The management of ASC-US in HIV-infected women is particularly problematic because the rates of ASC-US and HPV detection are 2 to 3 times greater than in HIV-negative women. In addition, the risk of CIN 2 and 3 is much higher.26 HPV testing as a triage for ASC-US is not efficient in immunosuppressed women because the majority of ASC-US Pap tests in these women are HPV-positive.
ASCCP recommends colposcopy referral of all immunosuppressed women with ASCUS Pap test, regardless of their CD4 count, HIV viral load, or anti-retroviral therapy.26
Managing ASC-H: First, colposcopy
Clearly, women with ASC-H test results face a greater risk for CIN 2,3 and should be referred for immediate colposcopy.
The ASC-H designation is uncommon, reported in 0.27% to 0.6% of all Pap tests,27,28 or approximately 1 in 10 Pap smears read as ASC.
In ALTS, HPV testing and histology results were compared for women with Pap tests categorized as equivocal LSIL (ASCUSL), ASCUS-H, and high-grade squamous intraepithelial lesion (HSIL) (TABLE 2).29 High-risk HPV DNA was detected in 86% of ASCUS-H liquid-based Pap tests and 69.8% of ASCUS-H conventional smears. CIN 2,3 was found in 40% of liquid-based ASCUS-H smears and in 27.2% of conventional ASCUSH smears. A 3-year retrospective review of ASC-H with follow-up at Johns Hopkins Medical Institutions determined that 49% of patients had no CIN or glandular lesions.28 Of the 51% with CIN, approximately half the lesions were CIN 1 and half were CIN 2,3.
Further management depends on whether CIN is detected (FIGURE 3). If no CIN is found, the ASCCP guidelines recommend that cytology, colposcopy, and histology be reviewed. If there is a change in the diagnosis—eg, if the Pap interpretation is revised to HSIL—the patient should be managed accordingly.11
If there is no change, the patient should be followed with repeat cytology at 6-and 12-month intervals or HPV testing at 12 months. Women having any repeat abnormal Pap test at a threshold of ASC-US or greater or a positive HPV test should undergo repeat colposcopy.
ASC-H is of greater risk than ASC-US, but it is not as risky as HSIL. Therefore, a surgical excision procedure in the absence of documented CIN 2,3 would not normally be indicated.11
FIGURE 3 Management of atypical squamous cells–cannot exclude high–grade squamous intraepithelial lesions (ASC-H)
HPV test as triage option would mean retooling the system
Cytologic management systems have traditionally involved follow-up by repeat cytology, colposcopy, and, when necessary, treatment. Adding another triage option—HPV testing—requires that this system be retooled.
The labs. This is not difficult when the laboratory interpreting the liquid-based Pap test is the same lab that performs the “reflex” HPV test, as this allows the ASC-US Pap test to be reported as HPV-negative or HPV-positive. However, if the HPV test must be performed in a separate reference laboratory, the results of the Pap and HPV tests will arrive separately, and the clinician must collate the 2 reports before relaying the result to the patient.
The patients. Remember than an HPV test is a test for a sexually transmitted disease. (So is the Pap test, although it has not traditionally been considered as such.) For that reason, I give all patients a written explanation of the rationale behind testing ASC-US Pap tests for HPV. This explanation includes 2 check-off options at the bottom of the sheet where patients can indicate whether they would prefer HPV testing or one of the other follow-up options.
Most patients elect the HPV option. Our Pap test requisitions also have a check-off portion that allows us to notify the lab of patients who wants an HPV test if the Pap is interpreted as ASC-US.
