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High-grade cervical lesions after vaccination against human papillomavirus: A Danish cohort study.

ABSTRACT: INTRODUCTION:It is pertinent to evaluate the impact of vaccination against human papillomavirus (HPV) in real life. The aim of the study was to evaluate the real-life impact of HPV vaccination in the first birth cohort of Danish women offered free HPV vaccination as girls and invited to screening at the age of 23 years. MATERIAL AND METHODS:Women born in 1993 were offered free HPV vaccination at the age of 15 years but women born in 1983 have never been offered free HPV vaccination. We followed these two birth cohorts for 10 years from the age of 15 to after their first invitation to screening, and compared the risk of high-grade cervical intraepithelial neoplasia (CIN). Data were obtained from Danish national health registers. RESULTS:Vaccination coverage was 91% in the 1993 birth cohort and <0.1% in the 1983 cohort. Screening coverage was close to 80% in both cohorts. CIN2+ was detected in 4% of the 15 748 screened women born in 1983 and in 3% of the 19 951 screened women born in 1993. The risk of high-grade CIN was reduced by about 30% in the 1993 cohort compared with the 1983 cohort; for CIN2+ relative risk 0.74 (95% CI 0.66-0.82) and for CIN3+ relative risk 0.68 (95% CI 0.58-0.79). CONCLUSIONS:This study investigated the real-life impact of quadrivalent HPV vaccination by comparing a cohort of women offered HPV vaccination with a cohort of women not offered HPV vaccination. The observed decrease in the detection of high-grade cervical lesions following HPV vaccination is in line with results from the randomized trials and has important implications for future cervical screening of HPV vaccinated cohorts.

SUBMITTER: Thamsborg LH

PROVIDER: S-EPMC7540379 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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High-grade cervical lesions after vaccination against human papillomavirus: A Danish cohort study.

Thamsborg Lise Holst LH Napolitano George G Larsen Lise Grupe LG Lynge Elsebeth E

Acta obstetricia et gynecologica Scandinavica 20200804 10

<h4>Introduction</h4>It is pertinent to evaluate the impact of vaccination against human papillomavirus (HPV) in real life. The aim of the study was to evaluate the real-life impact of HPV vaccination in the first birth cohort of Danish women offered free HPV vaccination as girls and invited to screening at the age of 23 years.<h4>Material and methods</h4>Women born in 1993 were offered free HPV vaccination at the age of 15 years but women born in 1983 have never been offered free HPV vaccinatio ...[more]

PMID: 32754966

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Project description:HPV16 accounts for 50-70% of cervical cancer cases worldwide. Characterization of HPV16 variants previously indicated that they differ in risks for viral persistence, progression to cervical precancer and malignant cancer. The aim of this study was to examine the association of severity of disease with HPV16 variants identified in specimens (n = 281) obtained from a Cervical Pathology and Colposcopy outpatient clinic in the University Hospital of Espírito Santo State, Southeastern Brazil, from April 2010 to November 2011. All cytologic and histologic diagnoses were determined prior to definitive treatment. The DNA was isolated using QIAamp DNA Mini Kit and HPV was detected by amplification with PGMY09/11 primers and positive samples were genotyped by RFLP analyses and reverse line blot. The genomes of the HPV16 positive samples were sequenced, from which variant lineages were determined. Chi2 statistics was performed to test the association of HPV16 variants between case and control groups. The prevalence of HR-HPV types in <CIN1, CIN2 and CIN3+ were 33.7%, 84.4% and 91.6%, respectively. Thirty-eight of 49 (78%) HPV16 positive samples yielded HPV16 sequence information; of which, 32 complete genomes were sequenced and an additional 6 samples were partially sequenced. Phylogenetic analysis and patterns of variations identified 65.8% (n = 25) as HPV16 European (E) and 34.2% (n = 13) as non-European (NE) variants. Classification of disease into CIN3+ vs. <CIN3 indicated that NE types were associated with high-grade disease with an OR = 4.6 (1.07-20.2, p = 0.05). The association of HPV16 NE variants with an increased risk of CIN3+ is consistent with an HPV16 genetically determined enhanced oncogenicity. The prevalence of genetic variants of HPV16 is distributed across different geographical areas and with recent population admixture, only empiric data will provide information on the highest risk HPV16 variants within a given population.

Project description:ObjectiveTo study the outcome of human papillomavirus (HPV) infection in women with cervical pathology results of non-cervical intraepithelial neoplasia (CIN) or cervical cancer and positive high-risk HPV test, as well as analyze the associated risk factors affecting the outcome of infection.MethodsTo investigate the outcome of high-risk (HR)-HPV infection in the female genital tract and analyze the associated risk factors affecting their outcome, a total of 196 women with positive HR-HPV test results and non-CIN or cervical cancer cervical pathology results were selected for follow-up at the Cervical Disease Clinic of the Obstetrics and Gynecology Hospital, Zhejiang University School of Medicine from January 2017 to March 2020. The follow-up interval was every 6 months, and both cervical cytology (TCT) and HR-HPV testing were performed at each follow-up visit. If the cervical cytology results were normal upon recheck and the HR-HPV test was negative, the woman was considered to be cleared of the HPV infection and was entered into the routine cervical screening population. When the repeat HR-HPV test remained positive after 6 months, the woman was defined as having a persistent HR-HPV infection. If HR-HPV persisted but the TCT results were normal, follow-up was continued. If HR-HPV persisted and the TCT results were abnormal, a colposcopy-guided biopsy was performed immediately. In this situation, if the histological results were still non-CIN or cervical cancer, the follow-up was continued. If the histological results confirmed the development of CIN or invasive cancer, then enter another study follow-up to further track its development and outcome, and the woman commenced the treatment process. The HPV infection clearance time was analyzed by the Kaplan-Meier method, and the comparison of the HPV clearance rate and infection clearance time between each of the different groups was performed using aχ2 test or Fisher's exact test, as appropriate. After the univariate analysis, several significant factors were included in the Cox model and independent risk factors were analyzed.ResultsA total of 163 women were enrolled in this study. The median age was 40.0 years (22-67 years) and the median follow-up time was 11.5 months (6-31 months). The spontaneous clearance rate of HR-HPV infection was 51.5%, and the median time to viral clearance was 14.5 months. Age and the initial viral load were high risk factors affecting the spontaneous clearance of HR-HPV infection. The factors significantly associated with HPV clearance rate and time to HPV clearance consisted of menopause and full-term delivery (P < 0.05).ConclusionsIn women with normal or low-grade lesions on the cell smear, the spontaneous clearance rate of HR-HPV infection was 51.5% and the time to clearance was 14.5 months. Age and the initial viral load were independent associated factors affecting the spontaneous clearance of HR-HPV infection in the female genital tract. These findings suggest that non-young women or those with high viral loads have a higher rate of persistent HR-HPV infection. Thus, intensive screening should be recommended.

Dataset Information

High-grade cervical lesions after vaccination against human papillomavirus: A Danish cohort study.

Publications

High-grade cervical lesions after vaccination against human papillomavirus: A Danish cohort study.

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