P11-07Genotyping of human papillomavirus in triaging of low-grade cervical cytology

11. Genotyping
M.P. CaƱadas 1, A. Tarrats 2, E. Duran 2, E. Martro 2, E. Castella 2, C. Lecumberri 2.
1Labco (Spain), 2Germans Trias i Pujol Hospital (Spain)

Background / Objectives

Atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intra-epithelial lesions (LSIL) are minor lesions of the cervical epithelium, detectable by cytological examination of cells collected from the surface of the cervix of a woman.Usually, women with ASCUS and LSIL do not have cervical (pre-) cancer, however a substantial proportion of them do have underlying high-grade cervical intra-epithelial neoplasia (CIN, grade 2 or 3) and so are at increased risk for developing cervical cancer. Therefore, accurate triage of women with ASCUS or LSIL is required to identify those who need further management.

The objective of the study was to evaluate whether typing of human papillomavirus among women with low-grade cervical cytology can improve the ability to identify women with cancer or cervical intrepithelial grade II+ (CIN II or worse)

 


Methods

This is prospective observational study carried out in Germans Trias i Pujol Hospital in Barcelona. A total of 266 women with low-grade cervical cytology participating in the study. 

We used residual liquid-based cytology samples for HPV genotyping. Extracted DNA was subjected to parallel polymerase chain reactions using three primer sets for HPV DNA amplification. HPV+ samples were genotyped by DNA sequencing.    

During 24 months, we study persistence and evolution of LSIL and ASCUS by citology and colposcopy each 6 months and HPV genotyping each year.

We study the individual and combined risk of progression depending on each HPV


Results

The adjusted prevalence of cervical intraepithelial neoplasia grade 2 or greater in our study was 23,5%. 

The odds of persistence and progression were higher in women infected with HPV 16, 18 and 31.

HPV 16 was detected in 40% of cases with CIN II or worse but only among 24% of all tested women. HPV 31 was detected in 20% of cases with CIN II or worde but only 11% among all tested women. Testing the three HPV types with higher risk (HPV16/18/31) detected 71% of CIN II or worse, with 36,9% testing positive. Positivity of other high risks HPV types had decreased risk of CIN III.


Conclusion

HPV genotyping may aid in prognosis of LSIL course. We should include HPV 31 en triaging LSIL, as is the second most frequent HPV type involved in progression.

Different high-risk HPV types confer different risks for the presence of CIN2 or worse, implying that genotyping could be a useful optimization of triaging strategies.


 


References

 

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Elfström KM, Smelov V, Johansson AL V, Eklund C, Naucler P, Arnheim-Dahlström L, et al. Long-term HPV type-specific risks for ASCUS and LSIL: a 14-year follow-up of a randomized primary HPV screening trial. Int J Cancer. 2015;136(2):350–9.

Wentzensen N, Bergeron C, Cas F, Vinokurova S, Von Knebel Doeberitz M. Triage of women with ASCUS and LSIL cytology: Use of qualitative assessment of p16INK4a positive cells to identify patients with high-grade cervical intraepithelial neoplasia. Cancer. 2007;111(1):58–66.

Solares C, Velasco J, Álvarez-Ruiz E, González-Fernández L, Encinas AI, Astudillo A, et al. Expression of p16/Ki-67 in ASC-US/LSIL or normal cytology with presence of oncogenic HPV DNA. Anticancer Res. 2015;35(11):6291–5.

Schiffman M, Solomon D. Findings to date from the ASCUS-LSIL Triage Study (ALTS). In: Archives of Pathology and Laboratory Medicine. 2003. p. 946–9.

Katki HA, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T, et al. Five-year risks of CIN2+ and CIN3+ for women with HPV-positive and HPV-negative LSIL Pap results.

Söderlund-Strand A, Eklund C, Kemetli L, Grillner L, Törnberg S, Dillner J, et al. Genotyping of human papillomavirus in triaging of low-grade cervical cytology. Am J Obstet Gynecol. 2011;