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Introduction: Although the incidence of squamous cell cervical cancers in the U.S. has markedly declined over time with the introduction of the Papanicolaou (Pap) test, the incidence of glandular cell cancers has increased. The sensitivity of detecting lesions containing abnormal glandular cells is much lower than that for lesions containing abnormal squamous cells. While AGC-grade cytology results represent <1% of all Pap test results reported annually in the U.S., up to 40% of them represent a corresponding high-grade lesion on the followup biopsy. Guidelines for managing AGC-grade cytology released in 2006 by the American Society for Colposcopy and Cervical Pathology include HPV testing. The purpose of this study was to determine the prevalence and genotype distribution of HPV in AGC-grade liquid-based cytology (LBC) specimens compared to control specimens negative for intraepithelial lesion or malignancy (NILM).

Methods: Quest Diagnostics provided de-identified case and control LBC specimens. Cases were women with AGC-grade LBC specimens collected between 2007- 2012. Controls were a sample of women with NILM-grade LBC specimens collected between 2011-2012. DNA was extracted from LBC specimens using the QIAamp MinElute Media Kit (Qiagen Inc.) and amplified by PCR using the Linear Array HPV Genotyping Kit (Roche Molecular Inc.). To compare HPV prevalence and genotype distribution between AGC-grade cases and NILM controls, we used multivariate logistic regression to generate age-adjusted odds ratios (ORadj) and 95% confidence intervals (CI).

Results: Fifty-three AGC-grade LBC specimens (mean age; 57 yrs, age range; 18-95 yrs) and 338 NILM LBC specimens (mean age; 45 yrs, age range; 20-91 yrs) were screened for 37 types of HPV DNA: 13 high-risk (HR) HPV types and 24 low-risk (LR) HPV types. Any HR-HPV was present in 34% of AGC-grade specimens and 7.4% of NILM specimens (ORadj=9.11; 95% CI: 4.08-20.33, p-value<0.001). When limited to HPV 16/18, at least one was present in 20.1% of AGC-grade specimens and 1.2% of NILM specimens (ORadj=40.10, 95% CI: 10.73- 149.88, p-value<0.001). In contrast, prevalence of low-risk (LR) HPV was similar between the two groups: 15% of AGC-grade specimens and 17.2% of NILM specimens (ORadj=0.91; 95% CI: 0.35-2.31, p-value=0.834).

Conclusion: AGC-grade specimens were found to contain a significantly higher rate of HR-HPV, especially HPV types 16 or 18 when compared to NILM specimens. These findings support the earlier recommendation that HPV testing should be performed on LBC specimens with AGC-grade diagnosis and suggests that genotyping may be a useful addition to the follow up testing being performed.


Presented at: George Washington University Research Days 2013.

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