A comprehensive natural history model of HPV infection and cervical cancer to estimate the clinical impact of a prophylactic HPV‐16/18 vaccine

Abstract

The object of our study is to project the impact of a prophylactic vaccine against persistent human papillomavirus (HPV)-16/18 infection on age-specific incidence of invasive cervical cancer. We developed a computer-based mathematical model of the natural history of cervical carcinogenesis to incorporate the underlying type-specific HPV distribution within precancerous lesions and invasive cancer. After defining plausible ranges for each parameter based on a comprehensive literature review, the model was calibrated to the best available population-based data. We projected the age-specific reduction in cervical cancer that would occur with a vaccine that reduced the probability of acquiring persistent infection with HPV 16/18, and explored the impact of alternative assumptions about vaccine efficacy and coverage, waning immunity and competing risks associated with non-16/18 HPV types in vaccinated women. The model predicted a peak age-specific cancer incidence of 90 per 100,000 in the 6th decade, a lifetime cancer risk of 3.7% and a reproducible representation of type-specific HPV within low and high-grade cervical precancerous lesions and cervical cancer. A vaccine that prevented 98% of persistent HPV 16/18 was associated with an approximate equivalent reduction in 16/18-associated cancer and a 51% reduction in total cervical cancer; the effect on total cancer was attenuated due to the competing risks associated with other oncogenic non-16/18 types. A vaccine that prevented 75% of persistent HPV 16/18 was associated with a 70% to 83% reduction in HPV-16/18 cancer cases. Similar effects were observed with high-grade squamous intraepithelial lesions (HSIL) although the impact of vaccination on the overall prevalence of HPV and low-grade squamous intraepithelial lesions (LSIL) was minimal. In conclusion, a prophylactic vaccine that prevents persistent HPV-16/18 infection can be expected to significantly reduce HPV-16/18-associated LSIL, HSIL and cervical cancer. The impact on overall prevalence of HPV or LSIL, however, may be minimal. Based on the relative importance of different parameters in the model, several priorities for future research were identified. These include a better understanding of the heterogeneity of vaccine response, the effect of type-specific vaccination on other HPV types and the degree to which vaccination effect persists over time. © 2003 Wiley-Liss, Inc. Key words: HPV; cervical cancer precursors; invasive cervical cancer; vaccine; modeling In the past several years there have been substantial advances in our understanding of the epidemiology of cervical carcinogenesis and the causal role of oncogenic human papillomavirus (HPV). [1][2][3] Despite this scientific progress, cervical cancer continues to have a devastating impact on women worldwide, with an estimated 400,000 women developing cervical cancer and 200,000 dying from this disease each year. 4 -7 From the perspective of developing countries, where less than 5% of women are ever screened, the development of a preventive vacci...

Efficacy of Pap Test in Combination with ThinPrep Cytological Test in Screening for Cervical Cancer

“…There are about 493,100 new cases of cervical cancer annually worldwide, and 273,000 women die of cervical cancer . Moreover, 80% of cervical cancer patients are found in underdeveloped countries (Goldie et al, 2003;American Cancer Society, 2008), which may be attributed to the low economic level and less use of screening.…”

Naturally processed and HLA‐B8‐presented HPV16 E7 epitope recognized by T cells from patients with cervical cancer

“…38 Most sexually active women are eventually exposed to HPV. 39 Although more than 95% of HPV infections of the anogenital tract resolve over 3-5 years, 40 cancer may develop in 3.7% of HPV16/18-infected individuals over their lifetime, 41 resulting in 470,000 new cases of cervical cancer globally each year. The importance of cell-mediated immune responses targeting HPV is supported by the fact that immunosuppression in transplant recipients 42 or patients infected with HIV 43 prevents the resolution of HPV infection and increases the risk of progression to malignancy.…”

Evidence of a higher prevalence of HPV infection in HTLV-1-infected women: a cross-sectional study

“…The absence of cervical cancer in this population could also be explained by the young age of patients, although cervical cancer may occur from the third decade of life; the peak age-specific cervical cancer is around the sixth decade of life 28 . Also, it was not possible to identify the HPV types involved in the infections or to determine whether this population has lower tissue viral clearance.…”

“…infection among HTLV-infected and uninfected groups when women were stratified into age ranges (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), 36-45, 46-55, and 56-65 years). Four positive cases of HPV infection (18.2%) were observed in HTLV-infected women with 46-55 years, whereas none was found in the control group at same age (p = 0.31) (data not shown).…”