HPV vaccination following loop electrical excision procedure (LEEP) for cervical intraepithelial neoplasia: A cost-effectiveness analysis (134)

Abstract

Objectives: Excisional cervical procedures, such as a Cold Knife Cone (CKC) or a loop electrical excision procedure (LEEP), are standard treatments for moderate to severe cervical intraepithelial neoplasia (CIN). Human papillomavirus (HPV) is the causal agent for CIN and can persist or recur; thus, patients can be susceptible to recurrent CIN following excision. Some data suggest that CIN recurrence rates decrease with HPV vaccination after LEEP. Here, we aimed to examine the cost-effectiveness of HPV vaccination following LEEP procedures compared with no vaccination. Methods: We constructed a decision-analytic model (TreeAge Pro 2021) to compare outcomes between patients who underwent LEEP followed by HPV vaccination with those who underwent LEEP without HPV vaccination. Our theoretical cohort contained 250,000 patients, the approximate number of patients who had LEEPs per year in the United States. Our outcomes were costs, quality-adjusted life-years (QALYs), any recurrence, recurrence of CIN 1, recurrence of CIN 2/3, number of pap smears, colposcopy, and second LEEP. We assumed that all individuals with any recurrence underwent a colposcopy and that all individuals who had a recurrence of CIN 2/3 would undergo a second LEEP. Probabilities of recurrence were based on a recently-published meta-analysis. All values were derived from the literature and discounted QALYs at a rate of 3%. Utilities were applied for four years after the initial LEEP procedure. Our cost-effectiveness threshold was $100,000/QALY. Univariate sensitivity analyses were performed to evaluate the robustness of the model. Results: In our one-year theoretical cohort of 250,000 patients who had undergone LEEP, the HPV vaccination strategy was associated with 17,281 fewer recurrences of CIN (8,360 cases of CIN 1 and 8,921 cases of CIN 2/3), 26,203 fewer pap smears (1,025,368 vs 1,051,570), 17,281 fewer colposcopies (20,588 vs 37,869), and 8,921 fewer second LEEP procedures (4,779 vs 13,701) (Table 1). The vaccination strategy was associated with a higher cost of $135 million. However, HPV vaccination was the cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of $29,180.81. In our sensitivity analyses, the HPV vaccination strategy remained cost-effective until the cost of the 3-dose HPV vaccine series reached $1,899.56, or the baseline (non-vaccinated) probability of recurrence was less than 4.8%. Objectives: Excisional cervical procedures, such as a Cold Knife Cone (CKC) or a loop electrical excision procedure (LEEP), are standard treatments for moderate to severe cervical intraepithelial neoplasia (CIN). Human papillomavirus (HPV) is the causal agent for CIN and can persist or recur; thus, patients can be susceptible to recurrent CIN following excision. Some data suggest that CIN recurrence rates decrease with HPV vaccination after LEEP. Here, we aimed to examine the cost-effectiveness of HPV vaccination following LEEP procedures compared with no vaccination. Methods: We constructed a decision-analytic model (TreeAge Pro 2021) to compare outcomes between patients who underwent LEEP followed by HPV vaccination with those who underwent LEEP without HPV vaccination. Our theoretical cohort contained 250,000 patients, the approximate number of patients who had LEEPs per year in the United States. Our outcomes were costs, quality-adjusted life-years (QALYs), any recurrence, recurrence of CIN 1, recurrence of CIN 2/3, number of pap smears, colposcopy, and second LEEP. We assumed that all individuals with any recurrence underwent a colposcopy and that all individuals who had a recurrence of CIN 2/3 would undergo a second LEEP. Probabilities of recurrence were based on a recently-published meta-analysis. All values were derived from the literature and discounted QALYs at a rate of 3%. Utilities were applied for four years after the initial LEEP procedure. Our cost-effectiveness threshold was $100,000/QALY. Univariate sensitivity analyses were performed to evaluate the robustness of the model. Results: In our one-year theoretical cohort of 250,000 patients who had undergone LEEP, the HPV vaccination strategy was associated with 17,281 fewer recurrences of CIN (8,360 cases of CIN 1 and 8,921 cases of CIN 2/3), 26,203 fewer pap smears (1,025,368 vs 1,051,570), 17,281 fewer colposcopies (20,588 vs 37,869), and 8,921 fewer second LEEP procedures (4,779 vs 13,701) (Table 1). The vaccination strategy was associated with a higher cost of $135 million. However, HPV vaccination was the cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of $29,180.81. In our sensitivity analyses, the HPV vaccination strategy remained cost-effective until the cost of the 3-dose HPV vaccine series reached $1,899.56, or the baseline (non-vaccinated) probability of recurrence was less than 4.8%.