Using cellular protein expression hpv test is better at detecting precancerous cervical lesions

Using cellular protein expression hpv test is better at detecting precancerous cervical lesions

An article published early online and in the October edition of The Lancet Oncology finds that using P16INK4A expression to test for human papillomavirus (HPV) - the virus associated with cervical cancer - has a greater sensitivity for detecting high-grade, precancerous cervical lesions than conventional cytology. The substudy, associated with the New Technologies for Cervical Cancer Screening (NTCC) study, also reports that this new test does not increase referral to colposcopy (a diagnostic procedure that provides a magnified view of the cervix and vaginal tissues).

Medical tests usually strive to maximize sensitivity and specificity - seeking a high percentage of true positives and a low percentage of false-positives, respectively. In detecting the potentially cancerous high-grade cervical intraepithelial neoplasia (CIN), it has been shown that HPV testing is more sensitive but less specific than conventional cytology; this leads to an increased referral rate for colposcopy. Since HPV testing can detect HPV DNA in cervical cells, it has high sensitivity. However, it has less specificity than cytology because HPV infections often regress without presenting any high-grade lesions.

To test whether HPV testing with triage according to overexpression of the cellular protein P16INK4A maintains the increased sensitivity and increases specificity of HPV testing compared with cytology, Dr Guglielmo Ronco (Centre for Cancer Prevention, Turin, Italy), Dr Francesca Carozzi (Centre for Cancer Study and Prevention, Florence, Italy) and colleagues from Italy and London conducted a substudy of women who were enrolled in the NTCC trial. The study utilized the fact that in healthy cells, P16INK4A is usually expressed in low concentrations, and in cervical-cancer cell lines, the protein is overexpressed because of HPV oncoprotein activity.

Cervical cell samples were collected from women who tested positive for presence of this virus, and 94% of the women underwent colposcopy. The researchers used immunostaining and histological analyses to test for P16INK4A overexpression in samples from 1170 women. Of the 1137 women whose results were available, 50 of had CIN grade 2 and 42 had CIN grade 3 or cancer.

Ronco and colleagues reported that the sensitivity of P16INK4A triage for HPV-positive women was 88% and the specificity of triage was 61%. That is, triage detected high-grade CIN in 81 of 92 women with HPV and correctly classified 633 of 1045 HPV-positive women as not having high-grade CIN, respectively. The sensitivity of HPV testing and P16INK4A triage for detecting CIN grade 2 or higher in women aged 35 to 60 years was significantly higher than for cytology. However, it is important to note that the frequency of referral to colposcopy did not differ between triage and conventional cytology. Similar results were found among women of 25 to 34 years pf age: sensitivity was also significantly higher for triage than for cytology and referral to colposcopy was about the same.

"Our data show that in HPV-positive women, P16INK4A overexpression is strongly associated with the presence of histologically confirmed CIN2+, suggesting that it actually is a marker of progression. This study supports the application of triage by P16INK4A immunostaining in HPV-positive women," concludes Dr. Ronco and colleagues.

Use of p16-INK4A overexpression to increase the specificity of human papillomavirus testing: a nested substudy of the NTCC randomised controlled trial

Francesca Carozzi, Massimo Confortini, Paolo Dalla Palma, Annarosa Del Mistro, Anna Gillio-Tos, Laura De Marco, Paolo Giorgi-Rossi, Giovanni Pontenani, Stefano Rosso, Cristina Sani, Catia Sintoni, Nereo Segnan, Manuel Zorzi, Jack Cuzick, Raffaella Rizzolo, Guglielmo Ronco, and the New Technologies for Cervival Cancer screening (NTCC) working group

The Lancet Oncology.


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The role of the p16 biomarker in cervical precancer (Video Medical And Professional 2018).

Section Issues On Medicine: Women health