Evidence of latent HPV infection in older Danish women with a previous history of cervical dysplasia

Author:

Hammer Anne123ORCID,Blaakaer Jan45ORCID,de Koning Maurits N. C.6,Steiniche Torben27,Mejlgaard Else7,Svanholm Hans8,Roensbo Mette T.9,Fuglsang Katrine1ORCID,Doorbar John10,Andersen Rikke H.8,Quint Wim G. V.6,Gravitt Patti E.11

Affiliation:

1. Department of Obstetrics and Gynecology Aarhus University Hospital Aarhus Denmark

2. Department of Clinical Medicine Aarhus University Aarhus Denmark

3. Department of Obstetrics and Gynecology Gødstrup Hospital Gødstrup Denmark

4. Department of Obstetrics and Gynecology Odense University Hospital Odense Denmark

5. Department of Clinical Research University of Southern Denmark Odense Denmark

6. DDL Diagnostic Laboratory Viroclinics‐DDL Rijswijk the Netherlands

7. Department of Pathology Aarhus University Hospital Aarhus Denmark

8. Department of Pathology Randers Regional Hospital Randers Denmark

9. Department of Renal Medicine Aarhus University Hospital Aarhus Denmark

10. Department of Pathology University of Cambridge Cambridge UK

11. Department of Epidemiology and Public Health University of Maryland School of Medicine Baltimore Maryland USA

Abstract

AbstractIntroductionUnderstanding whether human papillomavirus (HPV) may establish latency in the uterine cervix is important. A better understanding of HPV natural history is useful for clinical counseling of women attending screening and to accurately inform health prevention strategies such as screening and HPV vaccination. We evaluated the extent of latent HPV infections in older women with a history of abnormal cytology.Material and MethodsWe conducted a cross‐sectional study in Aarhus, Denmark, from March 2013 through April 2015. Women were enrolled if they underwent cervical amputation or total hysterectomy because of benign disease. Prior to surgery, women completed a questionnaire and a cervical smear was collected for HPV testing and morphological assessment. For evaluation of latency (i.e., no evidence of active HPV infection, but HPV detected in the tissue), we selected women with a history of abnormal cervical cytology or histology, as these women were considered at increased risk of harboring a latent infection. Cervical tissue underwent extensive HPV testing using the SPF10‐DEIA‐LipA25 assay.ResultsOf 103 women enrolled, 26 were included in this analysis. Median age was 55 years (interquartile range [IQR] 52–65), and most women were postmenopausal and parous. The median number of sexual partners over the lifetime was six (IQR 3–10), and 85% reported no recent new sexual partner. Five women (19.2%) had evidence of active infection at the time of surgery, and 19 underwent latency evaluation. Of these, a latent infection was detected in 11 (57.9%), with HPV16 being the most prevalent type (50%). Nearly 80% (n = 14) of the 18 women with a history of previous low‐grade or high‐grade cytology with no treatment had an active or latent HPV infection, with latent infections predominating. HPV was detected in two of the six women with a history of high‐grade cytology and subsequent excisional treatment, both as latent infections.ConclusionsHPV can be detected in cervical tissue specimens without any evidence of an active HPV infection, indicative of a latent, immunologically controlled infection. Modeling studies should consider including a latent state in their model when estimating the appropriate age to stop screening and when evaluating the impact of HPV vaccination.

Funder

Dagmar Marshalls Fond

Einar Willumsen Foundation

Kræftens Bekæmpelse

Sanofi Pasteur

Publisher

Wiley

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