How useful will be Human Papilloma virus testing in the prediction of HGSIL, AGS?? :

So will `HPV based screening test help tye community as a whole??

The identification of strong causal  relationship between persistent infection of the genital tract with high risk hpv types and occurrence of cervical pre cancer and cancer has resulted in the development of a number of screening tests based on hpt dna or rna detection systems. The four possible clinical applications of detecting high risk hpv dna are 1) as a primary screening test solely or in combination with cytology to detect cervical cancer precursors 2) as triage for women with cytology findings of ascus or lsil in order to select women who need referral for colposcopic diagnosis and treatment 3) in subsequent management of women referred for colposcopy due to abnormal smears but where findings on colposcopy /biopsy are negative and 4) as a follow up test for women treated for high grade cin with local ablative or excisional therapy in order to identify rapidly and accurately evaluate the treatment outcomes.

Hpv tests rely on molecular technologies that detect hpv dna in cervical /vaginal samples collected either by health care provider of self sampling. Hybrid capture technology is the most commonly used. Results from various studies highlight the accuracy of hybrid capture 2 for detecting high grade lesions . Results from one meta analysis with HC2 being used for primary screening demonstrated 23 % more detection of  cin 2 cin 3 or cancer compared to cytology at cut off ascus or lsil  but was 6 % less specific combined hpv and cytology screening results identification of further 4 % more cin 3 lesions but at the expense of 7 % loss in specificity, The pooled sensitivity of hc2 for finding underlying hsil was 89.3% but varied over as large range while the pooled specificity of hc2 in excluding hsil was 87.8% . Both the pooled sensitivity and specificity were higher for trials from north America and Europe as compared to trials from developing countries,.

HPV dna testing is considerably more sensitive but somewhat less specific than cytology at detecting high grade cin . The lower specificity is primarily due to the detection of transient infections that have not produced cytologic changes . Consequently it is suggested that hpv dna test which is more sensitive should be applied first to identify the hpv positive women . This should be followed by cytology which is a more specific test to determine their management. Managing hpv positive but cytology negative women is challenging current evidence suggest repeating screening with both cytology and hpv after one year for such women.

Several studies have shown that HPV negativity alone or in combination with negative cytology signifies a longer disease free interval against cin2+ than being negative for cytology alone. An over view of several meta analysis ans systematic trial reviews shows minimal over diagnosis from HPV testing for women aged over 30 years and the screening internal can be safely extended to at least 6 years with HPV DNA  testing for HPV negative  women.

The follow up results of a cluster randomised trial involving single round of screening in low resource setting demonstrates significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer with hpv testing. The investigators found it to be most objective and reproducible of all cervical screening tests and less demanding in terms of training and quality assurance. They concluded that with the availability of simple affordable and accurate hpv test it can be used as a primary screening approach in low resource settings for women who are at least 30 years of age.

Molecular techniques to detect hpv dna involve technologies that do not use amplification such as nucleic acid probe tests and those that utilize amplification such as polymerase chain reaction . Further amplification techniques are of three types target amplification target nucleic acids are amplified signal amplification signal generated from each probe is increased by a compound probe or branched probe technology and probe amplification probe molecule itself is amplified . Target amplified hpv assays amongst which pcr is the most common have capacity to detect very small amounts of hpv dna . In this method highly concentrated samples of a specific dna genetic sequence are produced which are then probed to identify the specific hpv genotypes present. PCR is usually inappropriate for large screening programmes in low resource setting because of the considerable skills equipment and costs involved in the procedure.