Baseline values and ranges for model variables
| Test/parameter | Base case | Sensitivity analysis |
| Screening/triage test performance (sensitivity/specificity to detect CIN2+) | ||
| Pap (primary)14 27 28 | 0.41/0.94 | Alternative sensitivity/specificity pair, 0.70/0.95 |
| CareHPV (primary), provider-collection of cervical samples14 | 0.78/0.89 | – |
| CareHPV (primary), self-collection of vaginal samples14 | 0.67/0.86 | – |
| VIA (triage of HPV+)14 33 34 36 37 | 0.60/0.75 | Alternative sensitivity/specificity pairs, 0.40/0.85 and 0.70/0.65 |
| Pap (triage of HPV+)14 33 35 38 | 0.85/0.55 | Alternative sensitivity/specificity pairs, 0.40/0.85 and 0.90/0.50 |
| Colposcopy performance (sensitivity/specificity to detect CIN1+)14 17* | ||
| Colposcopy (ASCUS+ women) | 0.95/0.68 | 1.0/1.0 |
| Colposcopy (HPV+ women ineligible for cryotherapy) | On ruling out cancer, all referred to treatment | 0.95/0.68, with <CIN1 sent back to routine screening intervals |
| Colposcopy (HPV+/VIA+ women ineligible for ST cryotherapy) | On ruling out cancer, all referred to treatment | 0.95/0.68, with <CIN1 sent back to routine screening intervals |
| Colposcopy (HPV+/Pap+ women) | On ruling out cancer, all referred to treatment | 0.95/0.68, with <CIN1 sent back to routine screening intervals |
| Coverage and compliance† | ||
| Access to routine screening, % of the target population6 | 70% | 50%–80% |
| Visit compliance, screening facility‡ | 85% | 40%–85% |
| Visit compliance, referral facility‡ | 40% | 40%–85% |
| Treatment eligibility and efficacy | ||
| Eligibility for screen-and-treat cryotherapy29 42 | ≤CIN1, 100%; CIN2, 85%; CIN3, 75% | ≤CIN1, 75%; CIN2, 60%; CIN3, 49% |
| Screen-and-treat cryotherapy cure rate (for HPV+ or HPV+/VIA+)30–32 | 92% | 75% |
| Proportion of women maintaining an HPV infection following cryotherapy43 | 15% | – |
| Treatment cure rate following colposcopy (LEEP for CIN2+; else cryotherapy)30 | 96% | 85% |
| Proportion of women maintaining an HPV infectionfollowing colposcopic diagnosis and treatment44 | 10% | – |
| Discount rate for costs and life-years | 3% | 0%–5% |
| Direct medical costs, screening and treatment of precancer (2015 US$)14 ‡ | ||
| Pap test | 7.26 | 3 |
| CareHPV test (provider-collection) | 11.96 | – |
| CareHPV test (self-collection) | 11.04 | 75%–125% of base case |
| VIA triage test | 4.19 | – |
| Colposcopy/biopsy | 19.91 | 6.91§ |
| Cryotherapy | 18.16 | 30.54¶ |
| LEEP | 68.36 | 75%–125% of base case |
| Women’s time and transportation costs (2015 US$)‡ | ||
| Transportation to screening facility (round trip) | 0.41 | 0%–50% of base case |
| Transportation to referral facility (round trip) | 2.81 | 0%–50% of base case |
| Wait time, screening facility | 0.48 | 0%–50% of base case |
| Wait time, referral facility | 1.75 | 0%–50% of base case |
| Transport time, screening facility | 0.82 | 0%–50% of base case |
| Transport time, referral facility | 3.10 | 0%–50% of base case |
| Programmatic costs, training (2015 US$)‡ | ||
| Healthcare personnel (careHPV) | 0.09 per woman screened with careHPV | 50%–150% of base case |
| Laboratory technicians (careHPV) | 0.04 per woman screened with careHPV | 50%–150% of base case |
| Outreach workers/auxiliary nurses(careHPV self-collection) | 0.08 per woman screened with careHPV (self collection) | 50%–150% of base case |
| Healthcare providers (VIA and cryotherapy) | 1.51 per woman receiving VIA and/or cryotherapy | 50%–150% of base case |
| Cost of cancer treatment (2015 US$) (rounded)29 | ||
| Local cancer | ||
| - Direct medical | 944 | |
| - Direct non-medical** | 197 | |
| - Women’s time†† | 346 | |
| Total | 1486 | 944–2229 (direct medical only; 150% of base case) |
| Regional and distant cancer | ||
| - Direct medical | 918 | |
| - Direct non-medical** | 390 | |
| - Women’s time†† | 640 | |
| Total | 1946 | 918–2920 (direct medical only; 150% of base case) |
Parameter values for sensitivity analysis were determined as follows: screening and triage test performance (cited literature), colposcopy performance (assumption), coverage and compliance (assumptions), treatment eligibility and efficacy (cited literature), discount rate (assumptions), direct medical costs (assumptions, with the exception of colposcopy and cryotherapy, which were based on ranges suggested by Scale-Up and START-UP data), women’s costs (assumptions), programmatic costs (assumptions) and cancer costs (assumptions).
*Test performance characteristics of colposcopy in the START-UP demonstration project were derived from the worst diagnosis of the local pathologist relative to the worst diagnosis by a quality control pathologist (gold standard); we applied the treatment threshold of CIN1 , although this was not the treatment threshold in START-UP. To derive test performance of colposcopy, we excluded histological classifications that were inadequate or with a histological classification other than negative, CIN1, CIN2, CIN3 or cancer. Because CIN1 is not a true underlying health state in the microsimulation model, performance of colposcopy in the model is based on the underlying health states of no lesion, HPV infection, CIN2 or CIN3. For a treatment threshold of CIN1, we weighted sensitivity of colposcopy for women with HPV based on the country-specific prevalence of CIN1 among women with HPV infections in the START-UP studies.
†Compliance is defined as the proportion of women who return for each clinical encounter, relative to the previous visit.
‡Unpublished data from the Scale-Up Nicaragua project. Further details on costing data are provided in the online supplementary appendix.
§In sensitivity analysis, we considered the direct medical cost of colposcopy to be equivalent to the cost of colposcopy alone, without biopsy.
¶In sensitivity analysis, we considered the direct medical cost of cryotherapy to include the upper bound of cryotherapy equipment costs (assuming the lowest number of women treated per year per facility, in Carazo, Chontales or Chinandega) and the upper bound of cryotherapy supply costs (assuming the lowest number of women treated per gas tank in any facility in Carazo, Chontales or Chinandega).
**Direct non-medical costs include transportation to a tertiary facility, temporary housing and meals.
††Includes woman’s time and support person’s time.
ASCUS+, atypical squamous cells of undetermined significance or higher; CIN1+, cervical intraepithelial neoplasia grade 1 or higher; CIN2+, cervical intraepithelial neoplasia grade 2 or higher; HPV, human papillomavirus; HPV+: human papillomavirus test positive; LEEP, loop electrosurgical excision procedure; Pap+: Pap test positive; ST, screen and treat; US$, 2015 US dollars; VIA, visual inspection with acetic acid; VIA+: visual inspection with acetic acid test positive.