In the Journals

HPV vaccination of girls dramatically reduces cervical disease

Photo of Tim Palmer
Tim Palmer

Vaccination of girls aged 12 to 13 years with the bivalent HPV vaccine in Scotland has resulted in a marked decline in preinvasive cervical disease, according to results of a study published in British Medical Journal.

Researchers also observed evidence of clinically relevant herd protection among unvaccinated women.

“Cervical screening programs are expensive to organize and implement and require uptake rates of around 70% to 80% to guarantee effectiveness. They also require regular attendance for screening,” Tim Palmer, FRCPath, clinical lead for cervical screening in Scotland and honorary senior lecturer in the division of pathology at University of Edinburgh, said in an interview with HemOnc Today. “These constraints effectively preclude most countries in the world — including those in which the burden of cervical cancer is greatest — from mounting the prevention that, hitherto, has been the only one available to them.”

Scotland’s national HPV immunization program, launched in in 2008, used the bivalent vaccine until 2012. The school-based program targeted girls aged 12 and 13 years and was supplemented with a 3-year catch-up program to age 18 years.

Scotland also has a national cervical screening program, for which women ages 20 to 60 years were eligible until June 5, 2016, when the age range increased to 25 to 64 years. The program provides screenings every 3 years until age 50 years, followed by every 5 years until age 65 years, with a 5-year extension if necessary for follow-up of abnormalities.

Palmer and colleagues extracted screening data from the Scottish Cervical Call-Recall System on 138,692 women born between Jan. 1, 1988 and June 5, 1996, who had a documented smear test result at age 20 years.

Data extracted included community health index number, postal code, date of birth, attendance, immunization status, cytology result, referral for colposcopy and related histological diagnosis.

Fewer than half of the women (46.2%) were unvaccinated, whereas 49.4% received all three doses of vaccine, 3% received two doses and 1.5% received one dose.

Effect of vaccination on cytology results and related histological diagnoses from first year of screening at age 20 years, which researchers calculated using logistic regression, served as the study’s primary outcome.

Results showed that compared with unvaccinated women born in 1988, vaccinated women born in 1995 and 1996 demonstrated an 89% (95% CI, 81-94) reduction in prevalence of grade 3 or worse central intraepithelial neoplasia, from 0.59% (95% CI, 0.48-0.71) to 0.06% (95% CI, 0.04-0.11).

Researchers also reported reductions of 88% (95% CI, 83-92) in prevalence of grade 2 or worse CIN, from 1.44% (95% CI, 1.28-1.63) to 0.17% (95% CI, 0.12-0.24), and 79% (95% CI, 69-86) in grade 1 CIN, from 0.69% (95% CI, 0.58-0.63) to 0.15% (95% CI, 0.1-0.21).

Vaccine effectiveness appeared correlated with younger age at vaccination, with an 86% (95% CI, 75-92) reduction in grade 3 or worse CIN among those aged 12 to 13 years compared with a 51% (95% CI, 28-66) reduction among those aged 17 years.

“Girls immunized at ages 12 to13 years are highly likely to be HPV naive, and the vaccine will be most effective in this situation,” Palmer told HemOnc Today. “Nevertheless, there is documented benefit to women who have already been exposed to HPV, as shown by the reduction in disease in the catch-up cohorts.”

Unvaccinated girls born in 1995 and 1996 appeared to benefit from “herd immunity,” Palmer added.

“The development of herd immunity is responsible for the absence of high-grade disease in unvaccinated women in the routine immunization cohort,” he said. “This is entirely in keeping with the changes in HPV prevalence reported by Kavanagh et al., which showed herd protection at a virologic level for HPV16 and HPV18. This has major implications for cervical cancer protection.”

The researchers cited several limitations to their study, including its restriction to women screened at age 20 years and possible overestimation of vaccine effectiveness. Study strengths included direct linkage of immunization status and screening outcomes data and the fact that data are from the screened population as opposed to a selected cohort.

Palmer said these results offer hope for HPV prevention in previously underserved countries.

“Effective HPV immunization is a game changer for them, and for the many young girls who otherwise would face a significant risk of dying of invasive cervical cancer in their 30s, leaving young families to fend for themselves,” Palmer told HemOnc Today. “Many of these countries already have cold chains in place for other vaccines, facilitating the introduction of HPV immunization.” – Jennifer Byrne

For more information:

Tim Palmer, FRCP, can be reached at timothy.palmer@nhs.net.

Reference:

Kavanaugh K, et al. Lancet Infect Dis. 2017;doi:10.1016/S1473-3099(17)30468-1.

Disclosures: Palmer reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Photo of Tim Palmer
Tim Palmer

Vaccination of girls aged 12 to 13 years with the bivalent HPV vaccine in Scotland has resulted in a marked decline in preinvasive cervical disease, according to results of a study published in British Medical Journal.

Researchers also observed evidence of clinically relevant herd protection among unvaccinated women.

“Cervical screening programs are expensive to organize and implement and require uptake rates of around 70% to 80% to guarantee effectiveness. They also require regular attendance for screening,” Tim Palmer, FRCPath, clinical lead for cervical screening in Scotland and honorary senior lecturer in the division of pathology at University of Edinburgh, said in an interview with HemOnc Today. “These constraints effectively preclude most countries in the world — including those in which the burden of cervical cancer is greatest — from mounting the prevention that, hitherto, has been the only one available to them.”

Scotland’s national HPV immunization program, launched in in 2008, used the bivalent vaccine until 2012. The school-based program targeted girls aged 12 and 13 years and was supplemented with a 3-year catch-up program to age 18 years.

Scotland also has a national cervical screening program, for which women ages 20 to 60 years were eligible until June 5, 2016, when the age range increased to 25 to 64 years. The program provides screenings every 3 years until age 50 years, followed by every 5 years until age 65 years, with a 5-year extension if necessary for follow-up of abnormalities.

Palmer and colleagues extracted screening data from the Scottish Cervical Call-Recall System on 138,692 women born between Jan. 1, 1988 and June 5, 1996, who had a documented smear test result at age 20 years.

Data extracted included community health index number, postal code, date of birth, attendance, immunization status, cytology result, referral for colposcopy and related histological diagnosis.

Fewer than half of the women (46.2%) were unvaccinated, whereas 49.4% received all three doses of vaccine, 3% received two doses and 1.5% received one dose.

Effect of vaccination on cytology results and related histological diagnoses from first year of screening at age 20 years, which researchers calculated using logistic regression, served as the study’s primary outcome.

Results showed that compared with unvaccinated women born in 1988, vaccinated women born in 1995 and 1996 demonstrated an 89% (95% CI, 81-94) reduction in prevalence of grade 3 or worse central intraepithelial neoplasia, from 0.59% (95% CI, 0.48-0.71) to 0.06% (95% CI, 0.04-0.11).

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Researchers also reported reductions of 88% (95% CI, 83-92) in prevalence of grade 2 or worse CIN, from 1.44% (95% CI, 1.28-1.63) to 0.17% (95% CI, 0.12-0.24), and 79% (95% CI, 69-86) in grade 1 CIN, from 0.69% (95% CI, 0.58-0.63) to 0.15% (95% CI, 0.1-0.21).

Vaccine effectiveness appeared correlated with younger age at vaccination, with an 86% (95% CI, 75-92) reduction in grade 3 or worse CIN among those aged 12 to 13 years compared with a 51% (95% CI, 28-66) reduction among those aged 17 years.

“Girls immunized at ages 12 to13 years are highly likely to be HPV naive, and the vaccine will be most effective in this situation,” Palmer told HemOnc Today. “Nevertheless, there is documented benefit to women who have already been exposed to HPV, as shown by the reduction in disease in the catch-up cohorts.”

Unvaccinated girls born in 1995 and 1996 appeared to benefit from “herd immunity,” Palmer added.

“The development of herd immunity is responsible for the absence of high-grade disease in unvaccinated women in the routine immunization cohort,” he said. “This is entirely in keeping with the changes in HPV prevalence reported by Kavanagh et al., which showed herd protection at a virologic level for HPV16 and HPV18. This has major implications for cervical cancer protection.”

The researchers cited several limitations to their study, including its restriction to women screened at age 20 years and possible overestimation of vaccine effectiveness. Study strengths included direct linkage of immunization status and screening outcomes data and the fact that data are from the screened population as opposed to a selected cohort.

Palmer said these results offer hope for HPV prevention in previously underserved countries.

“Effective HPV immunization is a game changer for them, and for the many young girls who otherwise would face a significant risk of dying of invasive cervical cancer in their 30s, leaving young families to fend for themselves,” Palmer told HemOnc Today. “Many of these countries already have cold chains in place for other vaccines, facilitating the introduction of HPV immunization.” – Jennifer Byrne

For more information:

Tim Palmer, FRCP, can be reached at timothy.palmer@nhs.net.

Reference:

Kavanaugh K, et al. Lancet Infect Dis. 2017;doi:10.1016/S1473-3099(17)30468-1.

Disclosures: Palmer reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.