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Cytopathology and More | Effectiveness of the HPV vaccine in Australia

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Mujtaba Husain, MD

January 2014—A school-based quadrivalent human papillomavirus vaccine program was introduced in Australia in April 2007 for 12- to 13-year-old girls. This program was also extended to 14- to 17-year-old girls in schools and to 18- to 26-year-old women in the community. The vaccination program has been highly successful, with uptake rates of 86 percent, 82 percent, and 75 percent for doses one, two, and three, respectively. Australia also has an established National Cervical Screening Program. Screening is recommended at age 18, or two years after the onset of sexual activity. This program is also effective, with 77 percent uptake of screening for 20- to 24-year-old women between 2007 and 2011.

There have been multiple publications from Australia on the effect of the population-based HPV vaccination program on cervical abnormalities. In 2011, the Victorian Cytology Service reported a 38 percent reduction of biopsy-proven high-grade lesions (CIN2, CIN3, and adenocarcinoma) in women less than 18 years, with reduction of detection rates from 0.85 percent to 0.22 percent in an ecological study (Lancet. 2011;377: 2085–2092). However, at that time, population-based cervical screening outcome databases could not be linked to the National HPV Vaccination Program Register data. In a subsequent study, data from eight sexual health services surveillance databases measured the effect of HPV quadrivalent vaccine on genital warts in men and women (BMJ. 2013;346:2042). The study period was 2004 to 2011, and pre- and post-vaccination detection rate ratios were compared. The study reported a decline of 92.6 percent in women 21 years and younger, with detection rates decreasing from 11.5 percent in 2007 (pre-vaccination) to 0.85 percent in 2011. Women aged 21 to 30 years also showed a significant decline. Interestingly, during the same study period, the detection rates of genital warts in men dropped significantly; 81.8 percent for age 21 years and under and 51.1 percent for age 21 to 30 years. Notably, the vaccination for 12- to 13-year-old boys with catch-up vaccination for 13- to 14-year-olds was nationally implemented at a later date, beginning in February 2013. This decrease in genital warts in males was attributed to the development of herd immunity in unvaccinated males.

In an Oct. 22, 2013 online publication (Gertig DM, et al. Impact of a population-based HPV vaccination program on cervical abnormalities: a data linkage study. BMC Med. 2013;11:227), the authors measured the effectiveness of HPV vaccination on cervical abnormalities. This study is remarkable in that, for the first time, the vaccination program register has been linked with the state-based cytology register in one Australian state, Victoria. The authors report on the vaccine effectiveness against cervical abnormalities in school-based young women (17 years of age or younger), and the hazard ratios for cervical abnormalities by vaccination status. The study compares 14,085 unvaccinated and 24,871 vaccinated women who underwent routine cytology screening between April 2007 and December 2011. Eighty-five percent of eligible women received the three recommended doses of the vaccine. Detection rate of biopsy-proven high-grade abnormalities (CIN2, CIN3, and AIS) was significantly lower for vaccinated women compared with that of unvaccinated women (4.8 percent versus 6.4 percent per 1,000 person-years), with an adjusted hazard ratio of 0.72. More importantly, vaccine effectiveness for women completing all three doses was 47.5 percent for CIN3+ histology.

In conclusion, the authors document remarkable effectiveness of the HPV vaccine against cervical cancer precursors in young women within five years of a school-based vaccination program and an additional benefit of virtually eliminating genital warts. The authors also predict additional effectiveness of the school-based vaccination program as more young women who are vaccinated before sexual debut enter the cytology screening program. Australia’s experience should serve as a successful demonstration project toward global eradication of cervical cancer with appropriate prioritization and synchronization of vaccination and screening efforts.
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Dr. Husain, a member of the CAP Cytopathology Committee, is professor of pathology, University of Central Florida—College of Medicine, Orlando.

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