The Potential Clinical and Economic Value of a Human Papillomavirus Primary Screening Test That Additionally Identifies Genotypes 31, 45, 51, and 52 Individually

Abstract

Background: Although current human papillomavirus (HPV) genotype screening tests identify genotypes 16 and 18 and do not specifically identify other high-risk types, a new extended genotyping test identifies additional individual (31, 45, 51, and 52) and groups (33/58, 35/39/68, and 56/59/66) of high-risk genotypes.

Methods: We developed a Markov model of the HPV disease course and evaluated the clinical and economic value of HPV primary screening with Onclarity (BD Diagnostics, Franklin Lakes, NJ) capable of extended genotyping in a cohort of women 30 years or older. Women with certain genotypes were later rescreened instead of undergoing immediate colposcopy and varied which genotypes were rescreened, disease progression rate, and test cost.

Results: Assuming 100% compliance with screening, HPV primary screening using current tests resulted in 25,194 invasive procedures and 48 invasive cervical cancer (ICC) cases per 100,000 women. Screening with extended genotyping (100% compliance) and later rescreening women with certain genotypes averted 903 to 3163 invasive procedures and resulted in 0 to 3 more ICC cases compared with current HPV primary screening tests. Extended genotyping was cost-effective ($2298-$7236/quality-adjusted life year) when costing $75 and cost saving (median, $0.3-$1.0 million) when costing $43. When the probabilities of disease progression increased (2-4 times), extended genotyping was not cost-effective because it resulted in more ICC cases and accrued fewer quality-adjusted life years.

Conclusions: Our study identified the conditions under which extended genotyping was cost-effective and even cost saving compared with current tests. A key driver of cost-effectiveness is the risk of disease progression, which emphasizes the need to better understand such risks in different populations.

Figure 1.

Model structure. A) Human papillomavirus (HPV) model states. B) HPV primary with and without extended genotyping patient management strategies. Note: AGC=atypical glandular cells; ASC-H=atypical squamous cells: cannot exclude high-grade squamous intraepithelial lesion; ASCUS= atypical squamous cells of undetermined significance; CIN=cervical intraepithelial neoplasia; FIGO=Fédération Internationale de Gynécologie et d'Obstétrique; hrHPV=high-risk HPV; HSIL=high-grade squamous intraepithelial lesion; ICC=invasive cervical cancer; LEEP=loop electrosurgical excision procedure; LSIL=low-grade squamous intraepithelial lesion; NILM=negative for intraepithelial lesion or malignancy. Co-testing consists of both HPV primary testing (with or without extended genotyping) and cytology. * indicates that women will undergo the same genotype test (with or without extended genotyping) every 5 years.

Figure 2.

Number of times women did or did not undergo a colposcopy in different health states for human papillomavirus (HPV) primary screening with partial genotyping and extended genotyping (patient management strategies 1-3). A) Number of times women with cervical intraepithelial neoplasia (CIN) 1-3 undergoes a colposcopy; B) Number of times women without CIN 1-3 (healthy or HPV-positive) undergoes a colposcopy; C) Number of times women with CIN 1-3 did not undergo a colposcopy. Patient management strategy 1: 31, 45, 33/58, 51, 52, 35/39/68 with any abnormal cytology results will go to colposcopy; and 56/59/66 with atypical glandular cells (AGC), atypical squamous cells: cannot exclude high-grade squamous intraepithelial lesion (ASC-H), or a high-grade squamous intraepithelial lesion (HSIL) on cytology will go to colposcopy. Patient management strategy 2: 31, 45, 33/58, 52 with any abnormal cytology results will go to colposcopy; and 51, 35/39/68, 56/59/69 with AGC, ASC-H, HSIL will go to colposcopy. Patient management strategy 3: 31, 45, 33/58 with any abnormal cytology results will go to colposcopy; and 51, 52, 35/39/68, 56/59/66 with AGC, ASC-H, HSIL will go to colposcopy.

Figure 3.

Acceptability curves of the cost-effectiveness of extended genotyping compared to partial genotyping. Plots show the percent of Monte Carlo trials with an incremental cost-effectiveness ratio (ICER) value less than or equal to a given willingness-to-pay threshold for extended genotyping when costing A) $43.33 and using patient management strategy 1, B) $75 and using patient management strategy 1, C) $43.33 and using patient management strategy 2, D) $75 and using patient management strategy 2, E) $43.33 and using patient management strategy 3, and F) $75 and using patient management strategy 3. Patient management strategy 1: 31, 45, 33/58, 51, 52, 35/39/68 with any abnormal cytology results will go to colposcopy; and 56/59/66 with atypical glandular cells (AGC), atypical squamous cells: cannot exclude high-grade squamous intraepithelial lesion (ASC-H), or a high-grade squamous intraepithelial lesion (HSIL) on cytology will go to colposcopy. Patient management strategy 2: 31, 45, 33/58, 52 with any abnormal cytology results will go to colposcopy; and 51, 35/39/68, 56/59/69 with AGC, ASC-H, HSIL will go to colposcopy. Patient management strategy 3: 31, 45, 33/58 with any abnormal cytology results will go to colposcopy; and 51, 52, 35/39/68, 56/59/66 with AGC, ASC-H, HSIL will go to colposcopy.

Figure 4.

Number of times women did or did not undergo a colposcopy in different health states for human papillomavirus (HPV) primary screening with partial genotyping and extended genotyping (patient management strategies 1-3) when increasing the probability of progression 2-4 times. A) Number of times women with cervical intraepithelial neoplasia (CIN) 1-3 undergoes a colposcopy; B) Number of times women without CIN 1-3 (healthy or HPV-positive) undergoes a colposcopy; C) Number of times women with CIN 1-3 did not undergo a colposcopy. Patient management strategy 1: 31, 45, 33/58, 51, 52, 35/39/68 with any abnormal cytology results will go to colposcopy; and 56/59/66 with atypical glandular cells (AGC), atypical squamous cells: cannot exclude high-grade squamous intraepithelial lesion (ASC-H), or a high-grade squamous intraepithelial lesion (HSIL) on cytology will go to colposcopy. Patient management strategy 2: 31, 45, 33/58, 52 with any abnormal cytology results will go to colposcopy; and 51, 35/39/68, 56/59/69 with AGC, ASC-H, HSIL will go to colposcopy. Patient management strategy 3: 31, 45, 33/58 with any abnormal cytology results will go to colposcopy; and 51, 52, 35/39/68, 56/59/66 with AGC, ASC-H, HSIL will go to colposcopy.