Enhancing the scope of conventional cervical cytology for detecting HPV infection

Abstract

Cervical neoplasia is attributed to a persistent Human Papilloma Virus infection. The Pap smear being the mainstay of cervical cancer screening in low-resource settings, we studied the nonclassical features which might indicate HPV infection. These included abortive koilocytes, mild dyskeratosis, parakeratosis, mild nuclear hyperchromasia, bi/multinucleation, measles cells, and keratohyaline-like granules. Two hundred and eight women with a satisfactory Pap smear and a Hybrid Capture II test were compared against the "HPV Gold Standard" for validation of the nonclassical signs. This was defined as one with any/all of the following: definite HPV-related lesions on Pap smear (LSIL and above), hrHPV positivity, and CIN I, or above on histology. The highest PPV and NPV were achieved by bi/multinucleation and mild nuclear hyperchromasia, respectively. The mean number of nonclassical signs for HPV Gold Standard-positive and -negative groups was 5.52 and 3.12 per smear, respectively (P < 0.0005). Abortive koilocytes, mild dyskeratosis, mild nuclear hyperchromasia, bi/multinucleation, parakeratosis, and diffuse keratohyaline granules had the best correlation with the gold standard (P < 0.05). Addition of nonclassical signs to established intraepithelial lesions on Pap smear increased the sensitivity from 52.31 to 59.10% and reduced the specificity from 100 to 98%. To maximize the benefit from grouping of these signs, various combinations were studied. The best was: abortive koilocytes, mild nuclear hyperchromasia, and bi/multinucleation. Another was abortive koilocytes, mild nuclear hyperchromasia, bi/multinucleation, and mild dyskeratosis. In conclusion, these signs proved useful for identifying HPV infection. Population-based studies are required to corroborate our findings.

A study of the relationship between nuclear contour thickening, nuclear enlargement and human papillomavirus infection in squamous cells

“…Therefore, it is possible that cytotechnologists are intuitively considering not only the increase in chromatin but also nuclear contour thickening as a criterion for distinguishing atypical cells from NILM. [18][19][20][21] Furthermore, we found that the smaller the area ratio of the nuclear enlarged cells, the greater the nuclear contour thickening. Therefore, to infer infection with high-risk HPV from the morphology in Pap test samples, it may be necessary to focus not only on cells with enlarged nuclei but also on nuclear contour thickening.…”

“…Additionally, while we showed significant differences between squamous cells with enlarged nuclei in ASC‐US and NILM cases, the nuclear area ratio difference was only about 0.30. Therefore, it is possible that cytotechnologists are intuitively considering not only the increase in chromatin but also nuclear contour thickening as a criterion for distinguishing atypical cells from NILM . Furthermore, we found that the smaller the area ratio of the nuclear enlarged cells, the greater the nuclear contour thickening.…”

Diagnostic Algorithm to Reflect Regressive Changes of Human Papilloma Virus in Tissue Biopsies

“…AKs were defined as superficial or intermediate cells that met only one or two of these conditions, showing some perinuclear cytoplasmic clearing, but lacking the large, sharply demarcated pNcH surrounded by a condensed cytoplasmic rim and nuclear atypia 12,13. The degree of AKs was coded according to the total number of AKs in the specific selected lesion as follows: 0, no AKs; 1, AK is ≥1 but <10; 2, AK is ≥10 but <20; 3, AK ≥20.…”

Isthmic‐vaginal smear cytology in the follow‐up after radical vaginal trachelectomy for early stage cervical cancer: Is it safe?

“…As already described in the literature, the correlation between both cytopathologists was poor as well as the sensitivity if compared with the PCR results. Authors focusing on the detection of HPV by cytomorphology alone reported better results; however, many cytomorphological features were applied in these studies …”