Human Papillomavirus-16 E6 Variants in Cervical Squamous Intraepithelial Lesions from HIV-Negative and HIV-Positive Women

Abstract

Am J Clin Pathol 2001;116(1):143–148 This group studied 48 human papillomavirus (HPV)-16–positive squamous intraepithelial lesions (SILs) from HIV-negative patients [16 low-grade SILs (LGSILs) and 32 high-grade SILs (HGSILs)] and 13 HPV-16-positive SILs from HIV-positive patients with AIDS (1 LGSIL; 12 HGSILs). After HPV typing, the entire HPV-16 E6 coding region was amplified and sequenced. They detected 12 HPV-16 E6 prototypes and four variants among the LGSILs in HIV-negative patients, and 15 HPV-16 E6 prototypes and 17 HPV-16 variants in the HGSIL group. The most prevalent variant of SIL types was European 350G, present in three and 13 cases, respectively. In three HGSILs and zero LGSILs, they found mixed infection by an HPV-16 E6 prototype and a variant. Two variants (one each in LGSIL and HGSIL) were of non-European lineage. The only LGSIL in HIV-positive patients had an HPV-16 E6 prototype; in the HGSILs, they found 8 HPV-16 E6-prototypes, four with mixed infection with HPV-31 and four variants, all European 350G. The higher proportion of HPV-16 E6 variants in HGSIL than in LGSIL in HIV-negative patients suggests a greater risk of progression. Comment: I present this article because it illustrates two things: First, while HPV typing is still looking for its role in the clinical management of abnormal Pap smears and cervical intraepithelial neoplasia, it is accepted by researchers as having a great prognostic significance in cervical disease. Second, the idea of HPV variants is puzzling to a simple practitioner like me. How much like HPV-16 does something have to be for it to be considered a variant rather than a distinct subtype? On what evidence was that decided? Will there be high-risk variants and low-risk variants of high-risk types and low-risk types? When I send an HPV type now for ASCUS triage, my report comes back as “low risk, either positive or negative and high risk, either positive or negative.” If the experts are sure “low-risk HPV” is a benign condition, why do they bother to report it? Is the technology we have now for HPV typing good enough to use in clinical decision making? Is it good enough to replace colposcopy, or, for that matter, the Pap smear? (TMJ)