HPV status in women with high-grade dysplasia on cervical biopsy and preceding negative HPV tests.
INTRODUCTION
A considerable number of patients with high-grade cervical lesions have undergone preceding human papillomavirus (HPV) tests with negative results. In the present study, we attempted to elucidate the factors potentially contributing to the findings by testing biopsied samples from these patients.


MATERIALS AND METHODS
Of the 1654 women with HPV testing and follow-up cervicovaginal biopsies from March 1, 2013 to June 30, 2014, 21 of 252 women (8.3%) with biopsy-confirmed high-grade squamous intraepithelial lesion (HSIL) or worse had had negative results from preceding high-risk (hr)HPV tests. The corresponding paraffin blocks were tested for HPV using the Cobas 4800 system, a DNA microarray against 40 HPV genotypes, and DNA sequencing.


RESULTS
HPV was detected in 20 (95%) of the 21 biopsies with HSIL or worse, including HPV16/18 in 4, non-16/18 hrHPV in 10, and non-hrHPV in 6. HPV59 and HPV45 were 2.2 times more frequently detected than HPV16/18 in these samples. One sample was negative for all 3 tests (5%).


CONCLUSIONS
Our study has demonstrated that 8.3% of women with biopsy-confirmed HSIL or worse had preceding test results that were negative for hrHPV. The vast majority of the biopsied samples had detectable HPV, primarily hrHPV genotypes (67%) with HPV59 and HPV45 predominance. This genotypic prevalence pattern was markedly different from those reported in the general population. Non-hrHPV genotypes contributed to 29% of the cases, and HPV-negative cases were rare. In addition to the limited Cobas testing panel and rare possible HPV-negative HSIL or worse, other possible contributing factors to the discrepancy include cytologic sampling, interference material, technical errors, and reduced L1 gene expression in high-grade lesions.
['Ge|Yimin|Y|', 'Mody|Roxanne R|RR|', 'Olsen|Randall J|RJ|', 'Zhou|Haijun|H|', 'Luna|Eric|E|', 'Armylagos|Donna|D|', 'Puntachart|Natu|N|', 'Hendrickson|Heather|H|', 'Schwartz|Mary R|MR|', 'Mody|Dina R|DR|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D005188:False Negative Reactions D005260:Female D061809:Human Papillomavirus DNA Tests D006801:Humans D008875:Middle Aged D030361:Papillomavirus Infections D000081483:Squamous Intraepithelial Lesions D002583:Uterine Cervical Neoplasms
HPV test High-grade cervical lesion Human papillomavirus Cervical cancer HPV-cytology co-testing Papanicolaou test