Minor Cytological Abnormalities and up to 7-Year Risk for Subsequent High-Grade Lesions by HPV Type.

Maria Persson,Joakim Dillner,Sonia Andersson,Sven-Erik Olsson,K Miriam Elfström,Craig Meyers

doi:10.1371/journal.pone.0127444

Maria Persson, Joakim Dillner + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0127444

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Journal: PloS one	Publication Date: Jun 17, 2015
Citations: 8	License type: CC BY 4.0

Affiliation: Karolinska University Hospital, Karolinska Institutet

Abstract

ObjectiveDiagnoses of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are common, but the corresponding risk of disease varies by human papillomavirus (HPV) status, complicating management strategies. Our aim was to estimate the longer-term risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with ASCUS/LSIL by age, HPV status, and genotype(s).MethodsA total of 314 women with ASCUS/ LSIL were followed for a median of 3.8 years. Baseline HPV status was determined by reflex testing and women with histologically confirmed CIN2+ were identified through linkage to the Swedish National Quality Register for Cervical Cancer Prevention. Cumulative incidence and hazard ratios were estimated to explore differences between index data and associations with CIN2+.ResultsIn total, 89 women (28.3%) developed CIN2+. High-risk (HR) HPV-positive women developed significantly more CIN2+ than HR-HPV-negative women (cumulative incidence 3.5 years after the index test: 42.2%, 95% CI: 32.5–53.5 for HPV16/18; 36.2%, 95% CI: 28.3–45.4 for other HR-HPV types; and 2.0%, 95% CI: 0.5–7.8 for HR-HPV-negative women; p<0.0001).ConclusionHPV status was of greatest importance in determining the risk of CIN2+. The risk was low among HPV-negative women during the first years of follow-up, suggesting these women could be followed less intensively. HPV16/18-positive women may need intensified follow-up as they showed the highest risk of CIN2+.

Highlights

Screening programs based on cervical cytology have significantly reduced the incidence and mortality of cervical cancer since their introduction in the 1960s [1,2,3]
High-risk (HR) human papillomavirus (HPV)-positive women developed significantly more CIN2+ than HR-HPV-negative women
high-risk human papillomavirus (HR HPV) positive women had a higher cumulative risk of CIN2+ 3.5 after the index test compared to HR HPV negative women: cumulative 42.2% for HPV16/18 and 36.2% for other HR HPV types compared to 2.0% for HR HPV negatives

Summary

Introduction

Screening programs based on cervical cytology have significantly reduced the incidence and mortality of cervical cancer since their introduction in the 1960s [1,2,3]. Most HPV infections regress spontaneously and only a minority become persistent. These persistent infections carry a substantial risk for progression to CIN, which may progress further to invasive cervical cancer [6,7,8]. HPV18 is the second most common genotype in squamous cervical cancer and is associated with adenocarcinoma or its precursor, adenocarcinoma in situ [10]. In contrast to squamous cervical cancer, incidence of adenocarcinoma continues to increase in developed countries despite cervical cytology screening program efforts [11]. HPV16 and are found in approximately 70% of squamous cervical cancer [12, 13]

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Conclusion