Correspondence

Type-Specific Testing for Human Papillomavirus

N Engl J Med 2003; 349:614-615August 7, 2003

Article

To the Editor:

In their article about the epidemiologic classification of human papillomavirus (HPV) types associated with cervical cancer, Muñoz et al. (Feb. 6 issue)1 emphasize that the association with cervical cancer varies according to the particular HPV type, ranging from a very strong association (a prevalence of HPV type 16 of 58.9 percent among women with squamous-cell cervical cancer) to a very weak association (a prevalence of HPV type 53 and others of 0.2 percent). However, infections with many HPV types are associated with minor abnormalities on Papanicolaou smear that are associated with a low risk of cancer; these abnormalities are called atypical squamous cells or low-grade squamous intraepithelial lesions.2 The likelihood that a Papanicolaou smear showing such abnormalities heralds cancer is approximately 1 in 1000.3

On the basis of the survey by Muñoz et al., we subdivided HPV types from a previous study4 into two groups: group A, consisting of HPV types that are associated with 0.9 to 58.9 percent of cervical cancers (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59), and group B, consisting of all other known HPV types that are associated with less than 0.9 percent of cervical cancers. HPVs without an assigned type were classified as unknown. For infections with multiple types, the category assigned reflected the type associated with the higher-risk group.

Table 1Table 1Distribution of Human Papillomavirus (HPV) Types According to the Cytologic Diagnosis. shows the distribution of these types in three categories of cytologic abnormalities, including minor (atypical squamous cells and low-grade squamous intraepithelial lesions) and major (high-grade) preinvasive cervical atypias.4 The proportions of these three types of cytologic abnormalities falling into group B were 36.7, 40.7, and 6.2 percent, respectively. Overall, 70 percent of cases of atypical squamous cells and 52 percent of cases of low-grade squamous intraepithelial lesions were either HPV-negative or were categorized in group B.4

These data indicate that a substantial percentage of abnormalities on Papanicolaou smear that are associated with a low risk of concurrent cancer are caused by HPV types that are rarely isolated from high-grade preinvasive cervical atypias or cervical cancers. Current practice guidelines recommend immediate colposcopic evaluation for women with smears containing both low-grade squamous intraepithelial lesions and high-grade preinvasive cervical atypia and do not recommend HPV testing for such women.5 The data in Table 1 indicate that this is sound practice for high-grade preinvasive cervical atypia, since group A HPV types predominate in these atypias and in cancers. However, the combination of a minor cytologic abnormality and a group B HPV may confer a sufficiently low risk of cancer that immediate referral for colposcopic evaluation is not necessary. In view of both the cost of colposcopic triage and the emerging use of HPV testing in primary screening, HPV-detection methods that provide a more precise measure of individual risk merit consideration. Given the data bases accrued in recent trials, it may be possible to determine the safety and feasibility of type-specific testing for HPV.2

Christopher P. Crum, M.D.
Brigham and Women's Hospital, Boston, MA 02115

5 References

1. 1

   Munoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003;348:518-527
   Full Text | Web of Science | Medline

2. 2

   Human papillomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. J Natl Cancer Inst 2000;92:397-402
   CrossRef | Web of Science | Medline

3. 3

   Cox JT. Management of atypical squamous cells of undetermined significance and low-grade squamous intra-epithelial lesion by human papillomavirus testing. Baillieres Best Pract Res Clin Obstet Gynaecol 2001;15:715-741
   CrossRef | Web of Science

4. 4

   Hughes SA, Sun D, Gibson C, et al. Managing atypical squamous cells of undetermined significance (ASCUS): human papillomavirus testing, ASCUS subtyping, or follow-up cytology? Am J Obstet Gynecol 2002;186:396-403
   CrossRef | Web of Science | Medline

5. 5

   Wright TC Jr, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ. 2001 Consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 2002;287:2120-2129
   CrossRef | Web of Science | Medline

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   Fabiola Medeiros, Liping Yuan, Gillian Breslin, Joshua Brodsky, Ashraf Saleemuddin, Sarah Feldman, Lynda Rushing, Aida Cviko, Kenneth R Lee, Christopher P Crum. (2005) Type-Specific HPV Testing as a Predictor of High-Grade Squamous Intraepithelial Lesion Outcome after Cytologic Abnormalities. Journal of Lower Genital Tract Disease 9:3, 154-159
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