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Estimate of the Global Burden of Cervical Adenocarcinoma and Potential Impact of Prophylactic Human Papillomavirus Vaccination


Estimate of the Global Burden of Cervical Adenocarcinoma and Potential Impact of Prophylactic Human Papillomavirus Vaccination

Jeanne M Pimenta et al. BMC Cancer.


Background: Data on the current burden of adenocarcinoma (ADC) and histology-specific human papillomavirus (HPV) type distribution are relevant to predict the future impact of prophylactic HPV vaccines.

Methods: We estimate the proportion of ADC in invasive cervical cancer, the global number of cases of cervical ADC in 2015, the effect of cervical screening on ADC, the number of ADC cases attributable to high-risk HPV types -16, -18, -45, -31 and -33, and the potential impact of HPV vaccination using a variety of data sources including: GLOBOCAN 2008, Cancer Incidence in Five Continents (CI5) Volume IX, cervical screening data from the World Health Organization/Institut Català d'Oncologia Information Centre on HPV and cervical cancer, and published literature.

Results: ADC represents 9.4% of all ICC although its contribution varies greatly by country and region. The global crude incidence rate of cervical ADC in 2015 is estimated at 1.6 cases per 100,000 women, and the projected worldwide incidence of ADC in 2015 is 56,805 new cases. Current detection rates for HPV DNA in cervical ADC tend to range around 80-85%; the lower HPV detection rates in cervical ADC versus squamous cell carcinoma may be due to technical artefacts or to misdiagnosis of endometrial carcinoma as cervical ADC. Published data indicate that the five most common HPV types found in cervical ADC are HPV-16 (41.6%), -18 (38.7%), -45 (7.0%), -31 (2.2%) and -33 (2.1%), together comprising 92% of all HPV positive cases. Future projections using 2015 data, assuming 100% vaccine coverage and a true HPV causal relation of 100%, suggest that vaccines providing protection against HPV-16/18 may theoretically prevent 79% of new HPV-related ADC cases (44,702 cases annually) and vaccines additionally providing cross-protection against HPV-31/33/45 may prevent 89% of new HPV-related ADC cases (50,769 cases annually).

Conclusions: It is predicted that the currently available HPV vaccines will be highly effective in preventing HPV-related cervical ADC.


Figure 1
Figure 1
Estimated proportion and number of new cervical ADC cases predicted in 2015 by region. Panel (a) shows estimated proportion of new cervical ADC cases among total invasive cervical cancer (ICC) cases predicted in 2015 by region. Panel (b) shows estimated number of new cervical ADC cases predicted in 2015 by region.
Figure 2
Figure 2
Age-standardized incidence of cervical ADC by region. Each bar represents the weighted average age-standardized incidence of cervical ADC for that region. Error bars show minimum and maximum values for individual countries within a region. Number in parentheses after region indicates number of countries contributing data. Incidence rates calculated using data from Cancer Incidence in Five Continents (CI5) Volume IX [reference 26].
Figure 3
Figure 3
Estimated percentage of cervical ADC versus estimated percentage of cervical screening coverage. Red circle, developed countries; blue square, developing countries; red dashed line = trend line for developed countries; blue solid line = trend line for developing countries; R2, coefficient of determination. R2 for all countries (regardless of whether designated as developed or developing) = 0.13.
Figure 4
Figure 4
Theoretical global impact of prophylactic HPV vaccination on cervical ADC, SCC and ICC. Panel (a) and panel (b) show future predictions, using 2015 data, of the proportion of new cases and number of new cases, respectively, of ADC (including ASC), SCC and ICC which could theoretically be prevented globally by a HPV vaccine efficacious against HPV-16/18, HPV-16/18/45 or HPV-16/18/45/31/33. Each bar represents the point estimate. The numbers to the right of each bar are the actual point estimates. The error bars represent the corresponding range of estimates calculated using the lower and upper bound limits of the confidence intervals from reported efficacy estimates (96.1% and 95.89% confidence intervals were used for estimates of HPV-16/18 associated vaccine efficacy for Cervarix® and Gardasil®, respectively, due to adjustments for multiplicity. 95% confidence intervals were used for estimates of vaccine efficacy against other HPV types). We assumed 100% vaccine coverage in these calculations.

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