The potential health and economic benefits of preventing recurrent respiratory papillomatosis through quadrivalent human papillomavirus vaccination

doi:10.1016/j.vaccine.2008.06.045

Vaccine

Volume 26, Issue 35, 18 August 2008, Pages 4513-4518

https://doi.org/10.1016/j.vaccine.2008.06.045 Get rights and content

Abstract

We estimated the health and economic benefits of preventing recurrent respiratory papillomatosis (RRP) through quadrivalent human papillomavirus (HPV) vaccination. We applied a simple mathematical model to estimate the averted costs and quality-adjusted life years (QALYs) saved by preventing RRP in children whose mothers had been vaccinated at age 12 years. Under base case assumptions, the prevention of RRP would avert an estimated $31 (range: $2–178) in medical costs (2006 US dollars) and save 0.00016 QALYs (range: 0.00001–0.00152) per 12-year-old girl vaccinated. Including the benefits of RRP reduced the estimated cost per QALY gained by HPV vaccination by roughly 14–21% in the base case and by <2% to >100% in the sensitivity analyses. More precise estimates of the incidence of RRP are needed, however, to quantify this impact more reliably.

Introduction

One of the potential benefits of quadrivalent human papillomavirus (HPV) vaccination is the prevention of recurrent respiratory papillomatosis (RRP), which can be caused by HPV types 6 and 11 [1], [2], [3]. Although RRP is rare, the health and economic burden per case of RRP can be substantial [4], [5].

The average age of diagnosis of juvenile-onset RRP is 4 years [4]. RRP usually manifests initially as hoarseness or voice changes, and less commonly, as respiratory difficulty attributable to papillomas in the airway [4]. Although surgery is often required to treat recurring papillomas in the respiratory tract, the lifetime number of surgeries varies substantially, from 2 to more than 100 [4], [5].

The purpose of this study was to estimate the potential reduction in the burden of RRP that can be achieved by quadrivalent HPV vaccination and to examine how the inclusion of RRP-associated benefits of HPV vaccination can influence estimates of the cost-effectiveness of quadrivalent HPV vaccination. Several cost-effectiveness studies of HPV vaccination in the United States have suggested that vaccinating 12-year-old girls would cost <$50,000 per quality-adjusted life year (QALY) gained, in the context of current cervical cancer screening in the United States [6], [7], [8], [9], [10], [11]. However, at the time this study was conducted, none of the published HPV vaccine cost-effectiveness studies included the potential benefits associated with preventing RRP. The inclusion of such benefits would be expected to result in more favorable estimates of the cost-effectiveness of HPV vaccination (i.e., a lower estimated cost per QALY gained).

To assess the potential benefits of preventing RRP through HPV vaccination, we focused on the benefits of preventing juvenile-onset RRP in children born to vaccinated mothers, and we estimated the averted direct medical costs of RRP and the gain in QALYs as a result of preventing RRP. We then examined how cost-effectiveness estimates of quadrivalent HPV vaccination might change when the benefits of preventing RRP were included.

Section snippets

Methods

We estimated the benefits of preventing juvenile-onset RRP in the children of vaccinated women. We focused on the strategy of quadrivalent HPV vaccination of 12-year-old girls in the United States, compared to the strategy of no vaccination. Our analysis focused on the costs and benefits of vaccinating a single cohort of 12-year-old girls, and these costs and benefits were calculated per girl vaccinated. We applied a health care payer perspective and included direct medical costs associated

Averted costs and QALYs saved per person vaccinated

Under base case assumptions, the prevention of RRP in children of vaccinated mothers would avert an estimated $31 in medical costs and save 0.00016 QALYs per 12-year-old girl vaccinated (Table 2). The estimate of the costs averted per person vaccinated was most sensitive to changes in the rate of RRP, and ranged from $5 to $89 when the lower and upper bound values for RRP were applied (Table 2). The estimate of the number of QALYs saved per person vaccinated was sensitive to changes in the rate

Discussion

We found that the inclusion of the potential benefits of preventing RRP in children of vaccinated mothers can change the estimated impact and cost-effectiveness of quadrivalent HPV vaccination of 12-year-old girls, although the magnitude of this change varied substantially. For example, under base case assumptions, the inclusion of RRP lowered the estimated cost per QALY gained by HPV vaccination by about 14% in the intermediate and high cost per QALY scenario and by about 21% in the low cost

Acknowledgement

The authors thank Elizabeth Unger, MD, PhD, for helpful comments.

References (29)

G.L. Freed et al.
Prevention of recurrent respiratory papillomatosis: role of HPV vaccination
Int J Pediatr Otorhinolaryngol
(2006)
M.J. Silverberg et al.
Condyloma in pregnancy is strongly predictive of juvenile-onset recurrent respiratory papillomatosis
Obstet Gynecol
(2003)
N.M. Bauman et al.
Recurrent respiratory papillomatosis
Pediatr Clin N Am
(1996)
R.A. Tasca et al.
Recurrent respiratory papillomatosis
Arch Dis Child
(2006)
M. Gabbott et al.
Human papillomavirus and host variables as predictors of clinical course in patients with juvenile-onset recurrent respiratory papillomatosis
J Clin Microbiol
(1997)
W.C. Reeves et al.
National registry for juvenile-onset recurrent respiratory papillomatosis
Arch Otolaryngol Head Neck Surg
(2003)
L.R. Armstrong et al.
Incidence and prevalence of recurrent respiratory papillomatosis among children in Atlanta and Seattle
Clin Infect Dis
(2000)
E.H. Elbasha et al.
Model for assessing human papillomavirus vaccination strategies
Emerg Infect Dis
(2007)
G.D. Sanders et al.
Cost-effectiveness of a potential vaccine for human papillomavirus
Emerg Infect Dis
(2003)
S.J. Goldie et al.
Projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 vaccine
J Natl Cancer Inst
(2004)

A.V. Taira et al.

Evaluating human papillomavirus vaccination programs

Emerg Infect Dis

(2004)

H.W. Chesson et al.

Cost-effectiveness of human papillomavirus vaccination in the United States

Emerg Infect Dis

(2008)

J.D. Goldhaber-Fiebert et al.

Cost-effectiveness of cervical cancer screening with human papillomavirus DNA testing and HPV-16, 18 vaccination

J Natl Cancer Inst

(2008)

Cited by (29)

Cost-effectiveness of nonavalent HPV vaccination among males aged 22 through 26 years in the United States
2018, Vaccine
In the United States, routine human papillomavirus (HPV) vaccination is recommended for females and males at age 11 or 12 years; the series can be started at age 9 years. Vaccination is also recommended for females through age 26 years and males through age 21 years. The objective of this study was to assess the health impact and cost-effectiveness of harmonizing female and male vaccination recommendations by increasing the upper recommended catch-up age of HPV vaccination for males from age 21 to age 26 years.
We updated a published model of the health impact and cost-effectiveness of 9-valent human papillomavirus vaccine (9vHPV). We examined the cost-effectiveness of (1) 9vHPV for females aged 12 through 26 years and males aged 12 through 21 years, and (2) an expanded program including males through age 26 years.
Compared to no vaccination, providing 9vHPV for females aged 12 through 26 years and males aged 12 through 21 years cost an estimated $16,600 (in 2016 U.S. dollars) per quality-adjusted life year (QALY) gained. The estimated cost per QALY gained by expanding male vaccination through age 26 years was $228,800 and ranged from $137,900 to $367,300 in multi-way sensitivity analyses.
The cost-effectiveness ratios we estimated are not so favorable as to make a strong economic case for recommending expanding male vaccination, yet are not so unfavorable as to preclude consideration of expanding male vaccination. The wide range of plausible results we obtained may underestimate the true degree of uncertainty, due to model limitations. For example, the cost per QALY might be less than our lower bound estimate of $137,900 had our model allowed for vaccine protection against re-infection. Models that specifically incorporate men who have sex with men (MSM) are needed to provide a more comprehensive assessment of male HPV vaccination strategies.
Recurrent laryngeal papillomatosis with oesophageal involvement in a 2 year old boy: Successful treatment with the quadrivalent human papillomatosis vaccine
2015, International Journal of Pediatric Otorhinolaryngology
Authors present a case report of a 2-year-old boy with recurrent laryngeal papillomatosis with oesophageal involvement due to human papilloma virus types 6 and 11, who needed surgical treatment every 4–6 weeks, altogether 11 times. After detailed immunological evaluation of basic immunological parameters, and in vitro detection of good responses to routine childhood immunization, a therapeutic vaccination has been decided with a 4-valent HPV vaccine. Following the third vaccine dose both laryngeal and oesophageal lesions disappeared completely, and for 2 years follow-up no papillomas could be detected. Vaccination could be a promising method in the treatment of RRP in children.
HPV vaccination in head and neck HPV-related pathologies
2014, Otolaryngologia Polska
Citation Excerpt :
Im wyższe jest miano przeciwciał u matki, tym skuteczniej przekazywane są przez łożysko noworodkowi. Szczepionka podana w celach terapeutycznych ma bezpośrednio wpłynąć na system immunologiczny i umożliwić skuteczniejszą kontrolę zakażeń wywoływanych przez HPV [48–52]. U wielu pacjentów ze świnką zauważono trwałą remisję rozlanych zmian brodawczakowych [49, 53].
Recent data demonstrate that human papilloma virus (HPV) plays a role in pathologies other than ano-genital cancers, specifically head and neck malignancies, and non-cancerous conditions such as recurrent respiratory papillomatosis (RRP). High-risk HPV16 and 18, and low risk HPV6 and 11 play the main role in HPV-related pathologies. As more and more information about the role of HPV infection in non-cervical diseases is amassed, additional questions about whether prophylactic HPV vaccines will effectively prevent these conditions are raised. HPV vaccination programs for the cervical pathology are being implemented worldwide. In the United States, the US Food and Drug Administration (FDA) approved the quadrivalent HPV vaccine for girls in 2006 and for boys in 2011. These vaccination programs were aimed at the genital, HPV-related lesions, and there was not much recognition at that time of how HPV vaccination programs might affect oral HPV infection, which is a risk factor for the development of HPV-related head and neck cancers. Vaccination has proved to be a successful policy, and an extant recommendation is aimed at preventing HPV and associated cervical and other anogenital cancers with the routine use of HPV vaccines for males and females. However, HPV vaccines are presently not recommended for preventing oropharyngeal cancer (OPC), although they have been shown to be highly effective against the HPV strains that are most commonly found in the oropharynx. This review is aimed at presenting the evidence-based knowledge concerning HPV vaccination and highlighting the trials and strategies for vaccine administration in HPV-dependent head and neck pathologies.
Cost-effectiveness and equity impacts of three HPV vaccination programmes for school-aged girls in New Zealand
2014, Vaccine
As with many high-income countries, vaccination coverage against human papilloma virus (HPV) infection is not high in New Zealand (NZ) at 47% in school-aged girls for three doses. We estimate the health gains, net-cost and cost-effectiveness of the currently implemented HPV national vaccination programme of vaccination dispersed across schools and primary care, and two alternatives: school-based only (assumed coverage as per Australia: 73%), and mandatory school-based vaccination but with opt-out permitted (coverage 93%). We also generate estimates by social group (sex, ethnic and deprivation group).
A Markov macro-simulation model was developed for 12-year-old girls and boys in 2011, with future health states of: cervical cancer, pre-cancer (CIN I–III), genital warts, and three other HPV-related cancers (oropharyngeal, anal, vulvar cancer). In each state health sector costs, including additional health sector costs from extra life, and quality-adjusted life years (QALYs) were accumulated.
The current HPV vaccination programme has an estimated cost-effectiveness of NZ$18,800/QALY gained (about US$9700/QALY gained using the OECD's purchasing power parities; 95% UI: US$6900 to $33,700) compared to the status quo in NZ prior to 2008 (no vaccination, screening alone). The incremental cost-effectiveness ratio (ICER) of an intensive school-based only programme of girls, compared to the current situation, was US$33,000/QALY gained. Mandatory vaccination appeared least cost-effective (ICER compared to school-based of US$117,000/QALY gained, but with wide 95% uncertainty limits from $56,000 to $220,000). All interventions generated more QALYs per 12-year-old for Māori (indigenous population) and people living in deprived areas (range 5–25% greater QALYs gained).
A more intensive school-only vaccination programme seems warranted. Reductions in vaccine price will greatly improve cost-effectiveness of all options, possibly making a law for mandatory vaccination optimal from a health sector perspective. All interventions could reduce ethnic and socioeconomic disparities in HPV-related disease.
Modeling the impact of quadrivalent HPV vaccination on the incidence of Pap test abnormalities in the United States
2013, Vaccine
We present data on Pap test results and HPV prevalence from the HPV Sentinel Surveillance project, a multiyear surveillance project enrolling women from a diverse set of 26 clinics throughout the US from 2003 to 2005. We use mathematical modeling to illustrate the potential timing and magnitude of decreases in Pap test abnormalities in sexually transmitted disease (STD), family planning, and primary care clinics in the US as a result of HPV vaccination.
The probability of an abnormal Pap result was based on three factors: (1) infection with HPV 16/18, or both; (2) infection with high-risk HPV types other than HPV 16/18; and (3) infection with HPV 6/11, or both. We estimated the relative reduction in the probability of an abnormal Pap result over the first 25 years of a female-only, quadrivalent HPV vaccination program, compared to a scenario of no HPV vaccination in which the probability of abnormal Pap results was assumed constant.
The probability of an abnormal Pap result ranged from 7.0% for the lowest risk group (those without any high-risk HPV types and without HPV 6/11) to 45.2% for the highest risk group (those with HPV 16/18 and at least one other high-risk HPV type). Estimated reductions in abnormal Pap results among women in the 21- to 29-year age group were 0.8%, 10.2%, and 11.3% in years 5, 15, and 25 of the vaccine program respectively, in the lower vaccine coverage scenario, and 7.4%, 21.4%, and 22.2%, respectively, in the higher coverage scenario.
Our results suggest that HPV vaccination will have a discernable impact on the probability of Pap abnormalities, but the timing and magnitude of the reduction will depend substantially on vaccine coverage and the degree of cross-protection against high risk HPV types other than HPV 16/18.
Recommendations for the diagnosis of human papilloma virus (HPV) high and low risk in the prevention and treatment of diseases of the oral cavity, pharynx and larynx. Guide of experts PTORL and KIDL
2013, Otolaryngologia Polska
Citation Excerpt :
In Thailand the same rate is estimated at 2.8 and remains 12 times higher than in European countries, whereas in Africa it is 4. In the USA nearly 1000 of new cases are diagnosed per 305 millions of people, and in the 62-million population of the United Kingdom 103 patients are under supervision of all ENT centres [79]. The confirmed presence of pointed or flat condylomas in the genital tract of a mother during a spontaneous labour increases the risk of RRP even 231 times when compared to cases without clinically apparent signs of infection [80].
The role of human papilloma viruses (HPV) in malignant and nonmalignant ENT diseases and the corresponding epidemiological burden has been widely described. International head and neck oncology community discussed growing evidence that oral HPV infection contributes to the risk of oro-pharyngeal carcinoma (OPC) and recommended HPV testing as a part of the work up for patients with OPC.
Polish Society of ENT Head Neck Surgery and National Chamber of Laboratory Diagnosticians have worked together to define the minimum requirements for assigning a diagnosis of HPV-related conditions and testing strategy that include HPV specific tests in our country. This paper briefly frames the literature information concerning low risk (LR) and high risk (HR) HPV, reviews the epidemiology, general guidance on the most appropriate biomarkers for clinical assessment of HPV. The definition of HPV-related cancer was presented. The article is aiming to highlight some of major issues for the clinician dealing with patients with HPV-related morbidities and to introduce the diagnostic algorithm in Poland.

View all citing articles on Scopus

View full text

Published by Elsevier Ltd.

The potential health and economic benefits of preventing recurrent respiratory papillomatosis through quadrivalent human papillomavirus vaccination

Abstract

Introduction

Section snippets

Methods

Averted costs and QALYs saved per person vaccinated

Discussion

Acknowledgement

Int J Pediatr Otorhinolaryngol

Obstet Gynecol

Pediatr Clin N Am

Recurrent respiratory papillomatosis

Arch Dis Child

Human papillomavirus and host variables as predictors of clinical course in patients with juvenile-onset recurrent respiratory papillomatosis

J Clin Microbiol

National registry for juvenile-onset recurrent respiratory papillomatosis

Arch Otolaryngol Head Neck Surg

Incidence and prevalence of recurrent respiratory papillomatosis among children in Atlanta and Seattle

Clin Infect Dis

Model for assessing human papillomavirus vaccination strategies

Emerg Infect Dis

Cost-effectiveness of a potential vaccine for human papillomavirus

Emerg Infect Dis

Projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 vaccine

J Natl Cancer Inst

Evaluating human papillomavirus vaccination programs

Emerg Infect Dis

Cost-effectiveness of human papillomavirus vaccination in the United States

Emerg Infect Dis

Cost-effectiveness of cervical cancer screening with human papillomavirus DNA testing and HPV-16, 18 vaccination

J Natl Cancer Inst