Abstract
Backgroundp16 immunohistochemistry is used to evaluate for HPV-associated cervical intraepithelial neoplasia. The diagnostic performance of p16 in HIV infection is unclear.MethodsBetween June-December 2009, HIV-infected women underwent Papanicolaou (Pap) smear, human papillomavirus (HPV) testing, visual inspection with acetic acid (VIA), and colposcopy-directed biopsy as the disease gold standard at a HIV clinic in Kenya. Pap smears were evaluated for p16 expression. Sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC) of p16 to detect CIN2/3 on histology and the impact of immunosuppression and ART was assessed.ResultsOf 331 cervical samples with p16 expression, p16 sensitivity and specificity to detect CIN2/3 was 54.1% and 72.4% respectively, which was lower than Pap and HPV in sensitivity, but higher in specificity than Pap, HPV, and VIA. Combining tests and p16 reduced sensitivity and increased specificity of Pap from 90.5% to 48.7% and 51.4% to 81.7%; of VIA from 59.5% to 37.8% and 67.6% to 89.9%; and of HPV from 82.4% to 50.0% and 55.3% to 84.8%. Combination p16 increased the PPV of Pap from 34.9% to 43.4%; of HPV from 34.7% to 48.7%; and VIA from 34.9% to 51.9%. Adjunctive p16 did not change AUC (P>0.05). P16 performance was not altered by immunosuppression or ART use. Combining p16 with HPV and VIA reduced the variation in HPV and VIA performance associated with CD4 and ART.ConclusionAs an adjunctive test in HIV-infected women, p16 immunohistochemistry increased specificity and PPV of HPV and VIA for CIN2/3, and was not altered in performance by immunosuppression, ART, or age.
Highlights
Cervical cancer is one of the most prevalent cancers worldwide with the greatest burden among women in resource-limited settings [1]
Of 331 cervical samples with p16 expression, p16 sensitivity and specificity to detect CIN2/3 was 54.1% and 72.4% respectively, which was lower than Pap and human papillomavirus (HPV) in sensitivity, but higher in specificity than Pap, HPV, and visual inspection with acetic acid (VIA)
Combining tests and p16 reduced sensitivity and increased specificity of Pap from 90.5% to 48.7% and 51.4% to 81.7%; of VIA from 59.5% to 37.8% and 67.6% to 89.9%; and of HPV from 82.4% to 50.0% and 55.3% to 84.8%
Summary
Cervical cancer is one of the most prevalent cancers worldwide with the greatest burden among women in resource-limited settings [1]. In resource-limited settings, cervical neoplasm screening is not routine and standard screening tools are not widely available [4]. HIV-infected women are disproportionately affected by HPV and at increased risk of developing HPV-associated cervical neoplasm and invasive cervical carcinoma [7, 8]. While HPV sensitivity has been shown to be high among HIV-infected women, HPV specificity is limited (55.7%) with further reductions associated with younger age, advanced immunosuppression, and shorter duration of antiretroviral therapy (ART) [5]. Due to the elevated risk of cervical neoplasm in HIV-infected women, alternative screening strategies including biomarkers for cervical cancer precursors/intraepithelial may improve early detection and prevent invasive cervical carcinoma
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