A study published online first in The Lancelot Oncology recommends that HPV (Human papillomavirus) testing should become the primary screening tool to rule out cervical cancer, with cytology reserved for triage of women who test positive for HPV, deciding which women need immediate colposcopy.
Testing for the two most dangerous strains of HPV - HPV16 and HPV18 - identifies more high-grade pre-cancerous lesions that can lead to cervical cancer, than using solely cytology for current cervical cancer screening.
An estimated 27% of women in the USA are infected with HPV, and although the best approach to manage the treatment for HPV infected women remains unclear, HPS DNA testing is widely known to be more effective than cytology-based primary cervical cancer screening.
The most common high-risk types of HPV are HPV 16 and 18, accounting for about 70% of invasive cervical cancer. HPV testing with HPV16 and HPV18 detection has been recommended as a triage technique in HPV-positive women to heighten the level of accuracy in identifying women with CIN3 or worse lesions (cervical cancer and its most serious precursor lesions) who require immediate colposcopy.
Researchers developed The ATHENA trial to evaluate the performance of HPV testing (including the detection of high-risk HPV strains 16 and 18) compared with liquid-based cytology, and to establish more effective management strategies for HPV-positive women.
The study was conducted on more than 47,000 women aged 25 years or older, who attended routine cervical screening in the USA between May 2008 and August 2009. Each woman had two samples taken to test for conventional cytology and HPV. A colposcopy referral was given to all women with atypical squamous cells of underdetermined significance (ASC-US) cytology or worse, to all those who had normal cytology but were HPV positive, and to a subset of women who tested negative for both.
HPV testing detected a considerably larger amount of existing high-grade pre-cancers in 92% of women who had colposcopy compared to 53.3 % who were given cytology.
Significantly, combining HPV testing with cytology was of little benefit compared with HPV testing alone, increasing sensitivity (the proportion of true positives correctly identified) by only 4.7%, but increasing the number of screen positives by more than a third.
The researchers also discovered potentially useful combinations of tests that could be used for triage of women with HPV infection, explaining that:
"The use of HPV16 or HPV18 detection as an additional or alternative triage strategy to reproducible cytological abnormalities (LSIL or worse, or HSIL or worse)...resulted in increased, more reliable (inter-laboratory) performance for identification of women with CIN3 or worse compared with the use of ASC-US or worse cytology alone."
They highlight that because the cobas HPV test identifies HPV16 and HPV18 and other cancer-causing HPV genotypes in one test, in comparison with cytology, testing for HPV16 and HPV18 to triage of women infected with HPV could be very efficient and reduce manpower requirements in laboratories.
The authors say in a concluding statement:
"Rational use of HPV testing (and genotyping for HPV16, or HPV18, or both) with or without liquid-based cytology can provide potentially cost-effective and safe cervical cancer screening."
Guglielmo Ronco from the Centre of Cancer Prevention in Turin, Italy and his colleagues pointed out in a comment, that:
"Co-testing of HPV and cytology will probably be replaced by standalone HPV testing as the primary screening test in high-income countries, because addition of cytology seems to provide little gain, according to Castle and colleagues' findings...and the results of longitudinal studies. The results also provide useful information about triage strategies for parts of the world where high-quality cytology has been difficult to implement and combinations of HPV tests might eventually offer a more sustainable option."