SS 13-04Human papilloma virus 35 is an aggressive subtype in long term follow up of equivocal (ASCUS) and low grade (LSIL) HPV positive cervical smears in Western Norway.

02. Epidemiology and natural history
O.K. Vintermyr 1, T. Bjørge 2, R. Skar 3, O.E. Iversen 4, H.K. Haugland 5.
1Department of Pathology, Haukeland University Hospital, Bergen. The Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen (Norway), 2Department of Global Public Health and Primary Care, University of Bergen, Bergen. (Norway), 3Department of Global Public Health and Primary Care, University of Bergen, Bergen. Cancer Registry of Norway, Oslo. (Norway), 4Department of Clinical Medicine, University of Bergen, Bergen. Women's Clinic, Haukeland University Hospital, Bergen. (Norway), 5Department of Pathology, Haukeland University Hospital, Bergen. (Norway)

Background / Objectives

A retrospective, population based study from Western Norway among women with equivocal (ASCUS) or low grade (LSIL) cell changes in the period 2006-2009 and with a positive HPV test in their first follow up (control) test. Women with prior (last two years) abnormal smear(s) and/or positive HPV tests, or lack of follow-up information were excluded.

All women were followed for 5-9 years with respect to progression (CIN2+/CIN3+) or remission.  


Methods

The high risk (hr)HPVsubtyping was done on stored Hybrid Capture (HC2) samples. For hrHPV subtyping a commercial multiplex PCR (f-HPV, Genomed LTD, UK) test was used that identifies essentially the same hrHPV subtypes as in HC2. A few samples with no definite HPV subtype in the f-HPV test were re- tested using standard Gp5+/GP6+ HPV PCR primers followed by DNA (Sanger) sequencing for HPV type identification.   

A relative hrHPV subtype estimate for risk of progression to CIN2+/CIN3+ was defined as the fraction of women with a specific hrHPV subtype that progress to CIN3+ versus the fraction that regress x 100 during the period of observation. The relative hrHPV subtype risk was compared with hrHPV negative and hrHPV negative/cytology negative (normal) women in a similar screening population cohort (1).


Results

A total of 804 women were HPV tested (16 samples were missing) and in 753 of these (93.7%) a specific hrHPV subtype (single or multiple) could be determined. Among these, only 61 women (7.4%) did not meet pre-set criteria for remission or progression by the end of 2014. The prevalence of HPV subtypes, in decreasing order, among women undergoing progression (CIN2+) and regression were: HPV16 (49%), 33 (18%), 52 (15%), 51 (9%), 35 (8%), 58 (8%), 39 (7%), 18 (6%), 31 (5%), 59 (5%), 45 (5%), 68 (3%), 56 (2%), 66 (1%) and HPV 16 (27%), 33 (12%), 52 (11%), 39 (11%), 58 (10%), 51 (9%), 18 (7%), 59 (6%), 56 (6%), 68 (5%), 45 (5%), 35 (5%), 31 (4%), 66 (3%), respectively. Relative hrHPV subtype progression risk to CIN 2+/CIN3+ was determined with respect to hrHPV type, dominant hrHPV type, single hrHPV types, and multiple hrHPV infections. HPV 16, 31, 33 and 35 were the most potent hrHPV types. For single hrHPV infections HPV 35 was as potent as HPV 16 for progression into CIN2+/CIN3+.


Conclusion

hrHPV 16 was the dominant HPV type in women undergoing progression and regression in delayed triage of HPV positive ASCUS/LSIL. HPV 35 was found in 5% of the lesions undergoing remission and in 8% of lesions progressing to CIN2+. For single hrHPV infections HPV 35 was as potent as HPV 16 to progress into high risk lesions.


References

Budal EB, et al. HPV DNA testing improves CIN2+ risk stratification and detection of CIN2+ in delayed triage of ASCUS and LSIL. A population-based follow-up study from Western Norway. Cancer Med., 2014, 3:182-9.