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HPV typing

Monday 28 November 2011

Type-specific surveillance of human papillomavirus (HPV) has been proposed as an early indicator of vaccine impact.

Longitudinal comparison of HPV typing results requires stable assays with high type-specific reproducibility. Assays are evolving and the impact of even minor changes in the assay format may be difficult to anticipate.

Studies designed to examine temporal trends in type-specific prevalence should archive residual material to permit retesting if assays change.

Tonsils

The presence of high-risk HPV in a minority of "normal" tonsillar tissues may confound assessment of the virus in oral/oropharyngeal squamous cell carcinoma biopsies using in vitro amplification methods. (21051999)

Cervical carcinoma

The demonstration of human papillomavirus (HPV) in 99.7% of cervical carcinoma surgical specimens from around the world required investigations by multiple alternative polymerase chain reaction (PCR) assays.

Cervical cytology

In a study, 752 of 799 (94.1%) abnormal and 82 of 300 (27.3%) normal cytology specimens tested HPV positive after PCR using GP5+/6+primers.

HPV genotype and prevalence estimates are dependent on the method(s) of detection and indicate that suboptimal analytical sensitivity for one or more of the less common high-risk HPV genotypes could lead to impaired clinical sensitivity.

HPV may be causal in almost every instance of abnormal cervical cytology; however, passenger HPV that is incidental to an abnormality may also have been detected.

Assays

 polymerase chain reaction (PCR)
 signal amplification
 HPV16 E6 PCR
 HPV16 E7 PCR
 HPV16/18 Invader assay was lower

Microarrays

A human papillomavirus (HPV) microarray system allows the determination of HPV type in clinical samples.

The presence of HPV can be determined in liquid-based Pap smears with the MyGene MyHPV Chip Kit HPV genotyping microarray test (MyGene Assay).

 Pap smears

  • 93 ThinPrep
  • 309 SurePath

Correlation of HPV DNA detection by the MyGene Assay with the Pap smear diagnosis showed a detection rate of 19/97 (19%) for normal Pap smears, 181/242 (74%) for atypical squamous cells of undetermined significance (ASCUS), and 61/63 (97%) for squamous intraepithelial lesions (SILs). (18382353)

The MyGene Assay and Hybrid Capture system gave equivalent results for all the categories studied, except for the presence of multiple infections, as determined by viral sequence analysis. (18382353)

Specifically, the Hybrid Capture system overestimated the presence of dual infection (low-risk and high-risk positive) by 48% and missed many cases of multiple infections, especially when 2 or more high-risk types were present. (18382353)

The MyGene Assay allows for the routine typing of HPV in liquid-based Pap smears, and that the presence of HPV DNA in ASCUS Pap smears is strongly correlated with a biopsy-proven SIL. (18382353)

Biomovies

 Oncogenic effects on the cell cycle and apoptosis of human papillomavirus (Animated)

References

 Impact of HPV assay on observed population prevalence. Unger ER, Steinau M, Lin JM, Patel SS, Swan DC. Diagn Mol Pathol. 2011 Jun;20(2):101-4. PMID: 21532491

 Comparison of molecular methods for detection of HPV in oral and oropharyngeal squamous cell carcinoma. Kingma DW, Allen RA, Caughron SK, Melby M, Moore WE, Gillies EM, Marlar RA, Dunn TS. Diagn Mol Pathol. 2010 Dec;19(4):218-23. PMID: 21051999

 HPV is detectable in virtually all abnormal cervical cytology samples after reinvestigation of HPV negatives with multiple alternative PCR tests. Evans MF, Adamson CS, Schned LM, St John TL, Leiman G, Ashikaga T, Cooper K. Diagn Mol Pathol. 2010 Sep;19(3):144-50. PMID: 20736743

 Correlation of Pap smear, cervical biopsy, and clinical follow-up with an HPV typing microarray system. Nuovo GJ, Bartholomew D, Jung WW, Han IK, Um T, Grabarz DF, Lee DJ, McCabe RT. Diagn Mol Pathol. 2008 Jun;17(2):107-11. PMID: 18382353