HPV Genotypes and Cervical Carcinoma: Analysis of 163 Cases in a US Population
RE Zuna, ST Dunn, JJ Johnson, RR Zhang, BA Bane, JL Walker, MA Gold, DS McMeekin, RA Allen. University of Oklahoma Health Sciences Center, Oklahoma City, OK
Background: This study examines the distribution of human papillomavirus (HPV) genotypes and the relative association with different histologic cell types in 163 invasive cervical cancers in a US population.
Design: Cervical cytologic samples were genotyped using the LINEAR ARRAY HPV Genotyping Test (Roche Diagnostics, Branchburg, NJ) that target the L1 gene using PGMY09/PGMY11 consensus primers. High risk (HR) HPV genotypes included HPV16, 18, 31 and 45. Other carcinogenic HPV genotypes were classed as intermediate risk (IR). HR-negative cases using this system were secondarily tested using PCR with HPV type-specific primers for E6 and LCR corresponding to HPV16, 18, 31, 33, 35, 39, 45, 52, 58 and 68.
Results: 153 histologically confirmed cancer cases were positive for one or more HR or IR HPV types using the PGMY09/PGMY11 primers. Of the 10 HPV-negative cases, 5 were subsequently shown to have HPV DNA using type-specific primers, including HPV16 (n=3), HPV18 (n=1) and HPV45 (n=1). After all analyses, 3.1 % remained HPV-negative.
HPV Genotypes in 163 Cervical CancersColumns total 100%
|CELL TYPE||SQUAMOUS N (%)||ADENO CA N (%)||ADENO SQ N (%)||SMALL CELL N (%)||TOTAL N (%)|
|HPV16||84 (67.7)||7 (33.1)||3 (30.8)||0||94 (57.7)|
|HPV18||14 (11.2)||9 (42.9)||7 (61.5)||4 (100)||34 (20.9)|
|HPV16+18||5 ( 4.0)||1 ( 4.8)||1 ( 7.7)||0||7 ( 4.3)|
|HR, NOT 16,18||6 ( 4.8)||2 ( 9.5)||1 ( 7.7)||0||7 ( 4.3)|
|IR||13 (10.4)||0||1 ( 7.7)||0||14 ( 8.6)|
|NO HPV||3 ( 2.4)||2 ( 9.5)||0||0||5 ( 3.1)|
The most frequent HPV genotypes associated with cancers other than HPV16 or 18 were HPV45 (4.3%) and HPV33 (2.4%). The association between HPV genotype and histologic cell type was highly significant (p <.001). HPV16 was closely associated with keratinizing squamous cancers while non-keratinizing cancers were more heterogeneous. IR genotypes were the highest risk genotypes in 8.6% of cancers.
Conclusions: This study documents the pattern of HPV genotypes in cervical cancers in a US population in the pre-vaccination era. HPV genotyping using PCR for L1 can fail to identify HPV DNA in a small percentage of cancers, likely due to loss/modification of L1 during integration. A small percentage of cancers remained HPV-negative after extensive HPV testing. Sampling variation may explain many of these cases.
Monday, March 9, 2009 1:00 PM
Poster Session II # 140, Monday Afternoon