Single visit approaches could revolutionize cervical cancer screening improving cancer prevention in low-resource, high-burden settings. In single visit approaches, treatment (usually cryotherapy) is provided based on a positive screening test. HPV testing is known to be the most sensitive test, but true point-of-care (POC) HPV tests, which are necessary to implement this approach, have not been available until now. Some have raised concerns that specificity of HPV testing may be too low, e.g. in HIVpositive women. Here we evaluate a new POC HPV test, including optimizing it for screen-and-treat.
At a colposcopy clinic and a primary care site in Cape Town, South Africa, 213 HIVnegative and 336 HIVpositive women, 30-65 years, were recruited. All women had a cervical sample collected that was tested by the Cepheid POC HPV test (detects 14 high-risk HPV types in 5 channels: HPV16, HPV18,45, HPV31,33,35,52,58, HPV51,59, HPV39,56,66,68) yielding a result within an hour. All women underwent colposcopy with histological sampling. Cervical intraepithelial neoplasia grade 2, 3 and cancer (CIN2+) and within normal limits were diagnosed based on consensus pathology review. Using logistic regression, we evaluated whether the clinical utility of the assay could be improved through reclassification of what was considered screen-positive based on HPV types and “viral load” estimated by cycle threshold (CT) values.
In HIVnegative women at the primary care site, 13.1% were positive for any of the 14 high risk types, biopsy-confirmed prevalence of CIN2+ was 4.0% and specificity was 89.2%. Specificity could be improved to 93.0% with no loss in sensitivity (88% for detection of CIN2+) if only HPV16,18,45,31,33,35,52,58 were tested for. In HIVpositive women, 47% were positive for any high risk HPV and prevalence of CIN2+ was 15.3%. Specificity improved to 71.6% with little loss in sensitivity (92.6% for CIN2+) testing only for HPV16,18,45,31,33,35,52,58. Combination of testing for a restricted number of genotypes and limiting CT values allowed specificity to be improved to 84.7% at a sensitivity of 85%; or specificity to 78% at a sensitivity of 90%.
For HIV-negative women, existing cutoffs on the HPV test, esp if restricted to some high risk types, make it an excellent test for screen-and-treat in South Africa. Given high sensitivity and specificity, even if treatment is based purely on the screening test result, number of women treated unnecessarily is small. For HIV-positive women, testing for only some genotypes and limiting the CT values allows for excellent sensitivity to be retained while attaining specificities that are adequate for single visit, screen-and-treat.