Cervical cancer is considered to be the delayed result of a sexually transmitted infection with particular high-risk carcinogenic HPV types.1 Cervical infection of a small minority of women progresses to asymptomatic high-grade pre-invasive dysplastic lesions, then eventually to invasive cancer. Pap smears screen for cell changes on the cervix that are abnormal due to the presence of HPV. Since about 40% of untreated high-grade lesions progress to invasive cancer within an average of 10 years, periodic screening using Pap tests has been very effective in identifying and enabling treatment of women with pre-invasive lesions. However, Pap screening is not perfect as in some settings women at high risk may not be screened routinely and variations in sampling techniques may lead to inaccurate Pap results. A recent Canadian study2 showed that most women (93.3%) had a normal Pap reading. Four percent of the women received a report of Atypical Squamous Cells of Undetermined Significance (ASCUS). A reading of Low-grade Squamous Intraepithelial Lesion (LSIL) was found in 2.3% and 0.3% were reported as High-grade Squamous Intraepithelial Lesion (HSIL). These data confirm rates reported by the Association for Reproductive Health Professionals (ARHP) in the USA.1
If a woman has an abnormal Pap test, there are options to be pursued depending upon how abnormal the Pap is. Women with ASCUS or LSIL are often managed by repeat Pap testing over four to six month intervals and those with repeat abnormal Paps usually will receive colposcopy. During colposcopy, after the application of vinegar, acetowhite areas on the cervix can be biopsied and examined for abnormal cell changes. Depending upon the degree of abnormality the patient may be treated surgically, chemically or with immunotherapy.
Another approach is to use the commercially available Hybrid Capture II test for the virus types responsible for pre-cancerous and cancerous cervical changes to help decision making for referring the high risk HPV positive cases to colposcopy and returning the HPV negative cases to routine Pap followup.3 Using the Hybrid Capture II kit from Digene, a cervical sample can be collected and transported to the laboratory where it will be tested for high risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68. The test can also be performed on a sample from a Thin Prep Pap collection. The test is sensitive to one picogram of HPV DNA.
There has been much debate about the usefulness and impact on costs of HPV testing.1,4,5 At this point in time, there may be at least 3 situations where HPV testing may contribute.
WHERE MIGHT HPV TESTING BE USEFUL?
1. Primary Screening: Most women become infected with HPV before 30-35 and resolve their infection. Because women are less likely to be high risk HPV positive when over the age of 30-35, an HPV test can be used with a Pap test to significantly decrease the risk of a false negative Pap result in this age group. ARHP proposes as a new development the following algorithm for primary HPV screening. 2
2. Triage After Pap: HPV triage testing can be used to determine which women with ASCUS (~ 40%), and perhaps those with LSIL (~ 70%) would be positive for high risk HPV and should receive colposcopy to identify the 10-15% who have an underlying high grade lesion.3,5
3. Post-Treatment Follow Up: Following treatment of the cervix for dysplasia caused by HPV the combination of a negative HPV test and negative Pap test is far more reassuring than a normal Pap alone, and approximately as sensitive as colposcopy.
Some European centers have already implemented scenarios 2 and 3 and are moving towards primary screening. At this stage in the development of strategies to use new viral testing technology to complement and enhance existing cervical cancer screening programs, these approaches should enable us to detect more cases, optimize the numbers of women subjected to colposcopy, reduce followup times which are accompanied by stress and concern, and increase our knowledge base for better detection and treatment.
References:
Association of Reproductive Health Professionals (ARHP) Clinical Proceedings Publication and Website Human Papillomavirus (HPV) and Cervical Cancer. March 2001.
Sellors J. et al. Prevalence and predictors of human papillomavirus infection in women in Ontario, Canada. CMAJ 2000;163(5):503-508.
Lytwyn A. et al. Comparison of human papillomavirus DNA testing and repeat Papanicolaou test in women with low-grade cervical cytologic abnormalities: a randomized trial. CMAJ 2000;163(6):701-707.
Kaufman RH, Adam E. Is human papillomavirus testing of value in clinical practice? Amer J Obstet & Gynecol 1999;180(5):1049-1053.
Solomon D, Schiffman M, Tarone B for the ALTS Group. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: Baseline results from a randomized trial. J Nat’l Canc Inst 2001;93(4):293-299.
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