A morphological protocol and guide-list on uterine cervix cytology associated to Papillomavirus infection

Abstract

The present study was designed to further assess the validity of the cytological description of morphological lesions said to be related to Papillomavirus (HPV) infections in senior women. The casuistic comprised 196 cervical smears from a group of women with no clinical or morphological evidence of neoplasia, collected simultaneously with samples submitted to detection of HPV DNA by PCR in a previous study. Three experienced cytologists studied each slide in two different conditions, with an interval of 20 months between them. The first approach was performed under routine laboratory standards, whereas the second was guided by a list of 16 well-defined parameters indicative of HPV-related cytological lesions. When suspicious cases of HPV-related alterations were grouped with positive cases, they showed on average: sensitivity of 25.5%, specificity of 84.4% and positive predictive value (PPV) of 26.8%. When suspicious cases were grouped with negative cases, sensitivity decreased, whereas specificity and PPV increased, as expected. In the second reading, which followed a "guide-list", a decrease in sensitivity was observed, contrasting with a sharp increase of positive predictive value. Among the 16 cytomorphological criteria tested, "koilocytosis", "mild koilocytosis" and "condylomatous parabasal cells" yielded the best predictive value for HPV DNA detection by PCR. In conclusion, despite the low sensitivity, cytopathologic assessment of cervico-vaginal smears leads to a highly specific diagnosis of HPV infection in menopausal women, with PPV of 91.0% when directed by a guide-list of well-defined morphologic criteria.

The Human Papillomavirus Type 16 E5 Oncoprotein Translocates Calpactin I to the Perinuclear Region

“…We have shown previously that E5 (in cooperation with HPV-16 E6) induces the formation of perinuclear vacuoles in HECs and HFKs grown in two-dimensional cultures (28). This vacuolization mimics the process of koilocytosis, a characteristic morphological change observed in HPV-infected keratinocytes in vivo (55). Because calpactin I promotes membrane fusion and is targeted to the perinuclear area by E5, we hypothesized that calpactin I might be involved in the observed vacuolization.…”

Cytomorphological Analysis of Uterine Cervical Pap Smears in Relation to Human Papillomavirus Infection in Indonesian Women

“…For the negative and ASCUS cases (with minimal abnormalities), HPV positivity was detected in 24 of 113 cases (21.2%). Yamamoto et al [12] reported HPV positivity in 18.2% of cytologically negative cases using classical and 14 nonclassical parameters. Schneider et al [13] have found an overall HPV positivity in 9.5% of asymptomatic women with cervical smears showing classical and nonclassical signs of HPV infection using in situ filter hybridization for HPV 6/11, HPV 16 and HPV 18, respectively.…”

“…All the cervicovaginal specimens were carefully and strictly reevaluated by two experienced cytopathologists (M.V., L.R.) determining the signs of cytopathic effects, including classical [10] and nonclassical [11,12,13,14,15] parameters. These parameters are summarized in table 1 and consist of koilocytosis, dyskeratosis-parakeratosis, mild koilocytosis, mild dyskeratosis-parakeratosis, binucleation, multinucleation, enlarged nuclei (mild, moderate, high) and hyperchromasia (mild, moderate, high) [10,11,12,13].…”

“…Cytomorphological evaluation of koilocytosis and dyskeratosis-parakeratosis could predict the presence of an HPV infection [10,11,12]. However, Schneider et al [13] reported that classical koilocytosis and dyskeratosis are not sensitive enough criteria for predicting the presence of an HPV infection.…”

“…However, Schneider et al [13] reported that classical koilocytosis and dyskeratosis are not sensitive enough criteria for predicting the presence of an HPV infection. Some studies have described cytological parameters including mild koilocytosis, mild dyskeratosis-parakeratosis, nuclear smudging, hyperchromasia, cleared cytoplasm, binucleation, multinucleation, macrocytosis, keratohyalin-like granules, measles cells, cytoplasmic folding and spindle nuclei as raising the predictive value of cytology for HPV infection [11,12,13,14,15,16]. …”