Elsevier

Vaccine

Volume 31, Issue 1, 17 December 2012, Pages 109-113
Vaccine

Impact of human papillomavirus (HPV) vaccination on HPV 16/18-related prevalence in precancerous cervical lesions

https://doi.org/10.1016/j.vaccine.2012.10.092Get rights and content

Abstract

Background

Vaccination against human papillomavirus (HPV) types 16 and 18 is recommended for girls aged 11 or 12 years with catch-up vaccination through age 26 in the U.S. Cervical intraepithelial neoplasia (CIN) grade 2 or 3 and adenocarcinoma in situ (CIN2+) are used to monitor HPV vaccine impact on cervical disease. This report describes vaccination status in women diagnosed with CIN2+ and examines HPV vaccine impact on HPV 16/18-related CIN2+.

Methods

As part of a vaccine impact monitoring project (HPV-IMPACT), females 18–31 years with CIN2+ were reported from pathology laboratories in CA, CT, NY, OR, TN from 2008 to 2011. One diagnostic block was selected for HPV DNA typing with Roche Linear Array. Demographic, abnormal Papanicolaou (Pap) test dates and vaccine status information were collected. The abnormal Pap test immediately preceding the CIN2+ diagnosis was defined as the ‘trigger Pap’.

Results

Among 5083 CIN2+ cases reported to date, 3855 had vaccination history investigated; 1900 had vaccine history documented (vaccinated, with trigger Pap dates, or unvaccinated). Among women who initiated vaccination >24 months before their trigger Pap, there was a significantly lower proportion of CIN2+ lesions due to 16/18 compared to women who were not vaccinated (aPR = .67, 95% CI: .48–.94). Among the 1900 with known vaccination status, 20% initiated vaccination on/after their trigger screening. Women aged 21–23 years were more likely to initiate vaccination on/after the trigger Pap compared to 24–26 year olds (29.0% vs. 19.6%, p = .001), as were non-Hispanic blacks compared to non-Hispanic whites (27.3% vs. 19.0%, p = .001) and publicly compared to privately insured women (38.1% vs. 17.4%, p < .0001).

Conclusion

We found a significant reduction in HPV 16/18-related lesions in women with CIN2+ who initiated vaccination at least 24 months prior to their trigger Pap. These preliminary results suggest early impact of the HPV vaccine on vaccine-type disease, but further evaluation is warranted.

Highlights

► We describe HPV vaccine status in women with precancerous cervical lesions. ► We examine HPV vaccine impact on HPV 16/18-related precancerous cervical lesions. ► 20% of women aged 18–31 years initiated HPV vaccination on/after abnormal Pap. ► Among women vaccinated >24 months before the abnormal Pap, there was a smaller percentage of lesions due to HPV 16/18.

Introduction

Human papillomavirus (HPV) types 16 and 18 account for about 70% of cervical cancers and 50% of precancerous lesions. Two prophylactic vaccines against HPV types 16 and 18 are licensed for use in females in the United States (U.S.) [1], [2]. In clinical trials, vaccine efficacy for the prevention of HPV 16 and 18-related precancerous lesions, cervical intraepithelial neoplasia grades 2 and 3 and adenocarcinoma in situ (CIN2+), was close to 100% for women naïve to the respective HPV vaccine types [3], [4], [5]. In contrast, efficacy ranged from 52% to 73% in the intent-to-treat (ITT) population that included women with prevalent HPV infections [3], [4], [5], as the vaccines are not therapeutic and do not prevent progression to disease among women infected with vaccine targeted HPV types at the time of vaccination. Since 2006, the U.S. Advisory Committee on Immunization Practices (ACIP) has recommended routine HPV vaccination for females aged 11 or 12 years, and for females aged 13–26 years if not previously vaccinated [6].

Monitoring trends in HPV type-specific CIN2+ could provide the earliest evidence of HPV vaccine impact on cervical disease, but population-based CIN2+ monitoring is challenging in the U.S. without national registries for cervical cancer screening or cervical precancerous lesions [7]. In Victoria, Australia, where vaccine coverage exceeds 80%, ecological data suggest vaccine impact on CIN2+ among females less that 18 years of age, but despite established registries, Pap and vaccine data linkage has been challenging, thus complicating interpretation of the data [8], [9]. Furthermore, since vaccination is recommended through age 26 years, many women may be vaccinated after exposure to HPV through sexual activity. Information on vaccination history including dates of vaccination is important for vaccine effectiveness studies. Obtaining such data is challenging in the U.S. because adolescent and adult vaccination history is often missing, incomplete or not collected in state-based Immunization Information Systems (IIS) [10].

The primary objective of this analysis was to describe vaccination status in women diagnosed with CIN2+ and to examine the impact of HPV vaccination on precancerous cervical lesions caused by HPV types 16 and 18, using the indirect cohort study design [11], [12]. This study design uses women with CIN2+ caused by non-HPV vaccine types as a comparison group to those infected with HPV vaccine types 16 and 18.

Section snippets

Population

We used data collected from the HPV-IMPACT project (described in detail elsewhere [13]), which was established in 2007 to monitor the population impact of the HPV vaccine on CIN2+ and HPV types in U.S. women. Archived diagnostic tissue for HPV DNA typing, HPV vaccination, cervical cancer screening history and demographic data were collected for females aged 18–39 years residing in 5 catchment areas in California, Connecticut, New York, Oregon and Tennessee who were diagnosed with CIN2+ and

Results

From 2008 to 2011, 5083 women aged 18–31 years with CIN2+ were reported to the monitoring system. At the time of analysis, vaccine history was investigated on 3855 (75.8%) of the 5083 eligible women. A total of 949 (24.6%) were classified as having initiated vaccination (of which, 821 women also had a trigger Pap date); 1079 (28.0%) were not vaccinated and 1827 (47.4%) had unknown vaccination history (Fig. 1). The proportion of investigated cases for whom vaccination history was unknown varied

Discussion

This analysis presents early data suggesting HPV vaccine impact on HPV 16/18-related CIN2+ lesions in women 18–31 years in the U.S. We used time interval between vaccination and abnormal Pap screening as a measure of the likelihood that the vaccination occurred prior to infection with the HPV type responsible for the lesion. Despite the small sample size, we found that among women who initiated vaccination at least 24 months before their trigger Pap, HPV 16/18 accounted for a significantly

Acknowledgements

The authors thank The HPV-IMPACT Working Group members for their dedication and contribution toward making this project successful: Ina Park, MD, MS, Erin Whitney, MPH, and Sharon McDonnell, MPH (California Department of Public Health, STD Control Branch); James Hadler, MD, Pamela Julian, MPH, James Meek, MPH (Yale University School of Medicine, Connecticut Emerging Infections Program) and Lynn Sosa, MD (Connecticut Department of Public Health); Mary Scahill and Denisse Licon, MPH (University

References (21)

There are more references available in the full text version of this article.

Cited by (73)

  • Effectiveness of catch-up human papillomavirus vaccination on incident cervical neoplasia in a US health-care setting: a population-based case-control study

    2018, The Lancet Child and Adolescent Health
    Citation Excerpt :

    However, vaccine effectiveness can be evaluated in girls and women who initiated the vaccine series at older ages. Evidence suggests vaccination has population effectiveness, which includes reduced prevalence of abnormal cervical cytology or HPV vaccine-type specific infections.2–9 Data from a randomised clinical trial10 of the quadrivalent HPV vaccine in India suggested that catch-up vaccination with fewer than three doses was both immunogenic and protective against HPV.

  • Cancer Prevention: Lessons Learned and Future Directions

    2016, Trends in Cancer
    Citation Excerpt :

    In terms of our ultimate goal of cancer prevention, the decreases in HPV prevalence have translated into reductions in the prevalence of downstream precancerous cervical lesions. Thus, vaccination against HPV types 16/18 resulted in a significant decrease in HPV 16/18-attributable lesions in women with pre-existing cervical intraepithelial neoplasia (CIN) 2 (diagnosed on abnormal Papanicolaou/Pap test; i.e., the ‘trigger’ Pap) who initiated vaccination at least 24 months before their trigger Pap [106,107]. This type-specific reduction in high-grade cervical lesions was apparent in women receiving at least one vaccine dose but not in unvaccinated women, suggesting an early impact of HPV vaccination on vaccine-type disease [107].

View all citing articles on Scopus
View full text