Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease

Abstract

Background: Information on human papillomavirus (HPV) type distribution is necessary to evaluate the potential impact of current and future HPV vaccines. We estimated the relative contribution (RC) to invasive cervical cancer (ICC) and precancerous cervical lesions of the nine HPV types (HPV 6/11/16/18/31/33/45/52/58) included in an HPV vaccine currently under development.

Methods: Estimations on ICC were based on an international study of 8,977 HPV positive cases and estimations on precancerous cervical lesions were extracted from a published meta-analysis including 115,789 HPV positive women. Globocan 2008 and 2010 World Population Prospects were used to estimate current and future projections of new ICC cases.

Results: RC of the 9 HPV types in ICC was 89.4%, with 18.5% of cases positive for HPV 31/33/45/52/58. Regional variations were observed. RCs varied by histology, ranging between 89.1% in squamous cell carcinomas (SCC) and 95.5% in adenocarcinomas (ADC). HPV 16/18/45 were detected in 94.2% of ADC. RC of the 9 types altogether decreased with age (trend test p < 0.0001), driven by the decrease in older ages of HPV 16/18/45. In contrast, the RC of HPV 31/33/52/58 increased with age. Due to population growth alone, projected estimates of ICC cases attributable to the 9 types are expected to rise from 493,770 new cases in 2012 to 560,887 new cases in 2025.The RCs of individual high risk HPV types varied by cytological and histological grades of HPV-positive precancerous cervical lesions, and there was an under representation of HPV 18 and 45 compared to ICC.

Conclusions: The addition of HPV 31/33/45/52/58 to HPV types included in current vaccines could prevent almost 90% of ICC cases worldwide. If the nine-valent vaccine achieves the same degree of efficacy than previous vaccines, world incidence rates could be substantially reduced.

Figure 1

Relative contribution of HPV 16/18/31/33/45/52/58 in cases of ICC HPV-positive, by histology. "ICC": Invasive cervical cancer; “SCC”: Squamous cell carcinoma; “ADC”: Adenocarcinoma; “ADSCC”: Adenosquamous cell carcinoma; “Other”: Includes undifferentiated, neuroendocrine, not otherwise specified, basal adenoid and cystic adenoid carcinomas. Additional information: Available data are from unvaccinated women (pre-vaccination period). Type specific relative contribution estimations: Numerator = single infections + proportional attribution of multiple types; Denominator = HPV DNA positive cervical cancer cases. The number of cases by histology is shown in “( )”. Specific information on HPV 6 and 11 is not included due to the low relative contribution of these types.

Figure 2

Relative contribution of HPV 16/18/45/31/33/52/58 and other types in ICC cases HPV-positive, by age group. "ICC": Invasive cervical cancer; Additional information: Available data are from unvaccinated women (pre-vaccination period). Type specific relative contribution estimations: Numerator = single infections + proportional attribution of multiple types; Denominator = HPV DNA positive cervical cancer cases. The number of cases by age group is shown in “( )”. Specific information on HPV 6 and 11 is not included due to the low relative contribution of these types.

Figure 3

Relative contribution of HPV 16/18/45/31/33/52/58 in precancerous cervical lesions HPV-positive, by histological and cytological diagnosis. “CIN1”: Cervical intraepithelial neoplasia grade 1; “CIN2”: Cervical intraepithelial neoplasia grade 2; “CIN3”: Cervical intraepithelial neoplasia grade 3 (including squamous carcinoma in situ); “ASCUS”: Atypical squamous cells of undetermined significance; “LSIL”: Low-grade squamous intraepithelial lesion; “HSIL”: High-grade squamous intraepithelial lesion; “RC”: Relative Contribution; “95%CI”: 95% Confidence Interval. Additional information: HPV type specific relative contribution: Numerator = includes either single or multiple infections, thus the total sum of % can exceed 100%; Denominator = ”Tested” cases that stands for the HPV/DNA positive cases from studies testing for the HPV type in question, thus denominators vary by type. The data source does not give specific information for HPV 6 and 11. 17. Data from Guan et al., IJC, 2012.