All women in at-risk demographic groups must receive cervical screening tests as soon as possible

Low coverage rates of women in at-risk demographic groups have been major causes for failures of Pap screening in LMICs.9 10 Political will for expanding public health services in LMICs is limited, and coverage of at-risk demographic groups is more readily achieved as costs for cervical screening tests decrease.10 Visual screening tests are inexpensive, but quality management is problematic. Disease-detection rates for visual screening were lower than disease-detection rates for no screening in the hands of visual screening experts funded by the US National Cancer Institute (NCI).11

Salary, supply and equipment costs for HPV tests and Pap smears are summarised in tables 1 and 2, respectively. Data in table 1 include prices negotiated through novel procurement strategies by the Clinton Health Access Initiative.12 The Pap smear is one of the most inexpensive of all medical laboratory tests. In the USA, where cytotechnologists earn ~US$90 000/year and pathologists earn ~US$5 00 000/year, data presented in table 2 imply that costs of salaries, supplies and equipment for a Pap smear total ~US$10. The US Centres for Medicare and Medicaid Services reimburses US$15.15 for a Pap smear,13 an amount that reimburses overhead costs (eg, laboratory space, administration and information systems) not included in either tables 1 and 2.

For decades, HPV screening has been advocated for LMICs. WHO advises that HPV self-sampling, which eliminates requirements for pelvic examinations, may contribute to acceptability and access to screening services.1 However, HPV experts who advocate HPV screening for LMICs acknowledge that HPV screening, whether clinician-collected or self-sampled, remains unaffordable for routine implementation in LMICs.14 The history of the Qiagen careHPV test is cautionary. Since 2004, with support from the Bill & Melinda Gates Foundation (BMGF), the careHPV test has been promoted as an HPV test affordable for LMICs. Supply costs for the careHPV test currently total at least US$10.(table 1) Data presented in tables 1 and 2 suggest that LMIC healthcare workers would receive US-level salaries to implement Pap smear screening for the same investment required to implement HPV screening with US$10 careHPV tests. In Myanmar, supply costs for each careHPV test are more than US$47 because the local distributor ‘added a larger profit than permitted’,15 illustrating challenges involved in negotiating stable prices for proprietary technology.

In 2013, WHO policy guidelines stated ‘In LMICs, because of the high cost of setting up Pap screening programmes, coverage of screening is very low and alternative screening methods are needed’,16 because ‘this traditional screening method requires highly trained human resources and a substantial amount of laboratory equipment’.16 The 2013 WHO assessment had been refuted in 2005, when the Head of Cancer Screening at the WHO International Agency for Research on Cancer (WHO/IARC), referring to a BMGF-funded study conducted in Osmanabad, India, emphasised ‘Our results clearly show that good-quality Pap smear screening can be implemented even in a rural setting of a developing country with reasonable investment, while HPV screening does not give any better [disease detection], despite the higher investments’.17 Data presented in tables 1 and 2 indicate that laboratory equipment costs for HPV tests exceed those for Pap smears. Technologists who analysed the 32 058 Pap smears collected in Osmanabad were trained for 3 months.18

All screening test results must be accurate

The most important performance characteristic of any cervical screening test is its biopsy-confirmed disease-detection rate, which is operator dependent and reliant on locality-specific quality management practices. Based largely on studies of HC2 HPV tests analysed in high-income countries with rigorous quality management practices, WHO/IARC determined that HPV tests yield 10%–20% higher disease detection rates but higher false-positive rates than Pap smears.19 HC2 HPV tests collected from women in China,20 Costa Rica21 and Zimbabwe22 and shipped to US reference laboratories for analysis demonstrated higher disease-detection rates but higher false-positive rates than Pap smears analysed in LMIC laboratories.

Two BMGF-funded studies illustrate the importance of using locality-specific disease-detection rate measurements, rather than measurements pooled from other settings, to inform transitions to HPV screening in LMICs. In the BMGF-funded Osmanabad study, which compared HC2 HPV tests analysed in India to Pap smears analysed in India, Pap smears outperformed HC2 HPV tests by demonstrating equivalent disease-detection rates with lower false-positive rates. In a separate BMGF-funded study, which compared Pap smears analysed in Mumbai to HC2 HPV tests analysed in Mumbai, Pap smears again demonstrated equivalent disease-detection rates with lower false-positive rates than HC2 HPV tests.23 Quality management practices used to assure good-quality Pap smears in India have not been detailed. Based on locality-specific measurements, transitioning from Pap smears to HC2 HPV tests in India would not be desirable because the transition would make cervical screening less accurate but more expensive.

Supplies for each HC2 HPV test are currently priced at US$53 (table 1).24 Quality management for HPV tests that become widely affordable in LMICs may prove more challenging than that for HC2. WHO/IARC advises ‘increased competition resulting in diminishing market share and reductions in the cost of testing might lead HPV test manufacturers to relax their standards of quality. Such a scenario could prove disastrous in many respects, since there are theoretically many more variables that can affect the performance of HPV testing than there are for Pap screening’.19 Today, more than 90% of HPV tests in the global market have not been evaluated in line with consensus requirements that ensure safe use.25

All women with abnormal screening test results must receive appropriate follow-up care

Without appropriate follow-up care, cervical screening is ineffective regardless the screening test used. Good follow-up of women with abnormal Pap smear results has been demonstrated in Cameroon (100% follow-up),26 China (95% follow-up),27 Costa Rica (97% follow-up),21 and Zimbabwe (98% follow-up).28 Quality management practices used to assure good follow-up in LMICs have not been detailed.

In South Africa, women with high-grade Pap smear results are usually lost to follow-up.29 Accurate biopsy-confirmed disease-detection rate measurements are not feasible in settings with low follow-up biopsy rates. It is imprudent to advocate transitioning from Pap screening to HPV screening in settings with low follow-up rates, because such transitions may make screening programmes more expensive but no more effective.

Combining visual screening tests with immediate cryotherapy assures 100% follow-up rates but introduces a quality management paradox.10 Visual screening experts emphasise that close monitoring of disease-detection rates is essential to maintain good standards of visual screening.30 Visual screening, when combined with immediate cryotherapy, produces no tissue biopsies with which to measure disease-detection rates.10 Current WHO guidelines recommend that visual screening programmes ‘transition rapidly’ away from visual screening ‘because of the inherent challenges with quality assurance’,31 but do not suggest destinations for that transition in settings where HPV screening is unaffordable.