Expression of p16INK4a and cervical infection with high-risk human papillomavirus are not related to p53 activity in cervical intraepithelial neoplasia

The objective of the study was to investigate the expression of p53 and p16INK4a in cervical intraepithelial neoplasia (CIN) and their relation with disease severity and high-risk human papillomavirus (HR-HPV) status. A series of 125 women with previous positive Pap smear were selected for this cross-sectional study. All patients underwent gynecological examination, including colposcopy. Specimens for Pap smears, Hybrid Capture 2 (HC2) test, and pathologic analysis were obtained. After evaluation of CIN grade, immunohistochemical detection of proteins p53 and p16INK4a was performed on paraffin-embedded sections. The extent of immunoexpression of both proteins was analyzed in relation to CIN grade and HR-HPV status. CIN was graded as 1 in 21, 2 in 17, and 3 in 87 specimens. p16INK4a positivity (at least 5% of epithelial cells stained) was found in 99 of 125 cases (79.2%) and was significantly higher in high-grade lesions as compared to low-grade CIN (P< 0.001). The expression of p53 did not differ across histologic strata. Protein expression neither of p16INK4a nor of p53 correlated with HR-HPV status. Expression of p16INK4a was not related with that of p53. Our study gives further support to previous findings of strong association of p16INK4a immunostaining with severity of epithelial atypia, but this protein may not be considered a predictor of HR-HPV status determined with HC2. By contrast, immunoexpression of p53 was related neither to CIN grade nor to HR-HPV status.

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Combining Human Papillomavirus Testing or Cervicography With Cytology to Detect Cervical Neoplasia

Archives of Pathology & Laboratory Medicine ◽

10.5858/2004-128-1257-chptoc ◽

2004 ◽

Vol 128 (11) ◽

pp. 1257-1262

Author(s):

Michelle Howard ◽

John W. Sellors ◽

Alice Lytwyn ◽

Paula Roth ◽

James B. Mahony

Keyword(s):

Human Papillomavirus ◽

Cervical Intraepithelial Neoplasia ◽

Intraepithelial Neoplasia ◽

Low Grade ◽

Invasive Squamous Cell Carcinoma ◽

Hpv Testing ◽

Cross Sectional ◽

Hpv Test ◽

Atypical Cells ◽

Sectional Analysis

Abstract Context.—Cervicography and oncogenic human papillomavirus (HPV) testing have been proposed for improving the accuracy of cervical cancer screening. Objective.—To examine whether cervicography and HPV testing can improve beyond chance the detection of cervical intraepithelial neoplasia (CIN) 2 or 3 in women with atypical cells of undetermined significance or low-grade squamous intraepithelial lesions on cytology. Design.—Cross-sectional analysis. Oncogenic HPV testing by Hybrid Capture II assay or cervicography combined with cytology was compared with the reference standard of colposcopy with directed biopsy. Setting.—Community family practices. Participants.—Three hundred four women with low-grade cytologic abnormality. Main Outcome Measures.—The gain in accuracy for detecting histologic CIN 2 or 3 or carcinoma. Because an adjunct test may improve sensitivity by chance alone, the sensitivity or specificity if the second test performed randomly was estimated. Results.—Cervical intraepithelial neoplasia 2 or 3 was found in 11.8% (36/304) of the women and invasive squamous cell carcinoma in 0.3% (1/304). The sensitivity of cytology for detecting CIN 2 or 3 was 73.0% and increased by 21.6% to 94.6% with the addition of a cervigram showing a low-grade lesion or higher or a positive HPV test result. These gains were reduced to 8.1% and 10.8% above the sensitivities expected if the additional tests performed randomly. The corresponding specificities decreased from 49.1% to 32.2% and 33.0%. There was insufficient power to determine whether observed sensitivities were statistically significantly higher than the expected sensitivities. Conclusion.—Adjunctive HPV testing or cervicography may provide similar gains in sensitivity, but they can appear misleadingly large if chance increases are not taken into account.

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High risk human papillomavirus type 16 and 18 infection in the cervical lesions of women with epithelial cell abnormality in Pap smear: A cytohistomorphologic association in Bangladeshi women

CytoJournal ◽

10.4103/1742-6413.115088 ◽

2013 ◽

Vol 10 ◽

pp. 14 ◽

Cited By ~ 6

Author(s):

Urmila Banik ◽

M. Shahab Uddin Ahamad ◽

Pradip Bhattacharjee ◽

Arun Kumar Adhikary ◽

Zillur Rahman

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Epithelial Cell ◽

Pap Smear ◽

Intraepithelial Neoplasia ◽

Cervical Lesions ◽

Cervical Intraepithelial Neoplasia Grade ◽

Cross Sectional ◽

Hpv 16 ◽

Hrhpv Type

Background: The aim of this study was to find out the extent of high-risk human papillomavirus (hrHPV) type 16/18 infection in the cervical tissue of women with epithelial cell abnormality in Pap smear and to establish an association between hrHPV type 16/18 infection and cytohistomorphology. Materials and Methods: A cross-sectional descriptive study was carried out in 1699 patients who went through Pap smear examination. Prevalence of epithelial cell abnormality was calculated. Forty eight of these women underwent routine histopathology and 47 were evaluated for human papillomavirus (HPV) type 16/18 by polymerase chain reaction assay. Results: Total 139 women revealed epithelial cell abnormality. Histopathology showed simple inflammation to malignancy. HPV type 16/18 infection was detected in 40.42% (19/47) of the patients. Individually type 16 and 18 were positive in 7 (14.9%) cases each and dual infection with type 16 and 18 were seen in 5 (10.6%) cases. While cervical intraepithelial neoplasia grade 1 (CIN 1) and < CIN 1 lesions showed 18.75% (3 out of 16) and 35% (7 out of 20) positivity respectively, ≥CIN 2 lesions revealed positivity of 81.82% (9 out of 11). Eighty percent HPV 16/18 positivity was seen in women of < 30 years of age. Conclusion: The findings of this study will contribute to HPV 16/18 knowledge in Bangladesh that will be useful in assessing the success of current vaccines with limited type spectra and augmenting cervical cancer screening strategies.

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Interactions between serum folate and human papillomavirus with cervical intraepithelial neoplasia risk in a Chinese population-based study

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy160 ◽

2018 ◽

Vol 108 (5) ◽

pp. 1034-1042 ◽

Cited By ~ 3

Author(s):

Jing Yang ◽

Aimin Yang ◽

Zhe Wang ◽

Wei Wang ◽

Zhilian Wang ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Cervical Intraepithelial Neoplasia ◽

Dose Response ◽

Intraepithelial Neoplasia ◽

Serum Folate ◽

Inverse Association ◽

Cross Sectional ◽

Folate Concentration ◽

High Risk Hpv

ABSTRACT Background Although folate deficiency has long been implicated in cancer development, uncertainties remain concerning its role in cervical cancer prevention. In particular, the interaction between human papillomavirus (HPV) and folate in the risk of cervical intraepithelial neoplasia (CIN) has been little studied. Objective The goal of this study was to evaluate the dose-response association of serum folate with the risk of CIN, and the potential for HPV to modify the risk of CIN. Design We performed a cross-sectional analysis of screening data in 2304 women aged 19–65 y who participated in an ongoing cohort of 40,000 women in China. Both categoric and spline analyses were used to evaluate the dose-response relation between serum folate and CIN risk. Results After adjusting for potential confounders, a statistically significant inverse association between serum folate concentration and at least grade 2 CIN (CIN2+) risk was observed (1st quartile compared with 4th quartile: OR = 1.40; 95% CI: 1.09, 1.79; P-trend < 0.01); however, serum folate concentration was not associated with CIN1 risk. The risk patterns are similar when limited to only CIN2 and CIN3. An inverse linear relation between increased serum folate concentration and the risk of higher-grade CIN (CIN2, CIN3, and CIN2+) was also observed (for CIN2+: P-overall < 0.01, P-nonlinearity = 0.96). The highest risk of CIN2+ was observed in women with high-risk HPV types, who also had the lowest serum folate concentrations (P-interaction < 0.01). Conclusions Our study indicates that serum folate is inversely associated with the risk of higher-grade CIN in Chinese women either with or without high-risk HPV infection. Thus, maintenance of normal serum folate levels may prove important for reducing the risk of CIN in women.

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Human Papillomavirus Distribution in Women with Abnormal Pap Smear and/or Cervical Intraepithelial Neoplasia in Vaccination Era. A Single-Center Study in the North Italian population

Microorganisms ◽

10.3390/microorganisms9040729 ◽

2021 ◽

Vol 9 (4) ◽

pp. 729

Author(s):

Barbara Gardella ◽

Mattia Dominoni ◽

Cecilia Sosso ◽

Anna Arrigo ◽

Andrea Gritti ◽

...

Keyword(s):

Human Papillomavirus ◽

Cervical Intraepithelial Neoplasia ◽

Pap Smear ◽

Prevalence Ratio ◽

Intraepithelial Neoplasia ◽

Pap Smears ◽

Low Grade ◽

Italian Population ◽

The North ◽

Hpv Types

Time trends prevalence of human papillomavirus (HPV) genotypes including negative and untypable infections were analyzed during a 15-year period (2005–2019) among 5807 subjects with abnormal pap-smears and/or cervical intraepithelial neoplasia (CIN). The rates of HPV16 dropped by 13% every 3 years (Prevalence Ratio, PR = 0.87, 95% CI = 0.82–0.93) in the CIN1 biopsy, while HPV16 status was unchanged over time in the CIN2+ biopsy. In CIN1 lesions, there was a corresponding increase of HR-HPV types unrelated to nonavalent vaccine. The rates of HPV 18, 31, and 52, decreased by 35% (PR = 0.65, 95% CI = 0.54–0.79), 19% (PR = 0.81, 95% CI = 0.73–0.91), and 21% (PR = 0.79, 95% CI = 0.73–0.86) every 3-year interval in CIN2+, respectively. Overall, the prevalence of negative/untypable HPV specimens in the entire database increased from 9.6% (129/1349) in the period 2011–2013 to 17.6% (161/913) and 28.4% (224/790) in the 2014–2016 period and in the 2017–2019 period, respectively (PR = 1.69,95% CI = 1.52–1.88). HPV 16 prevalence decreased significantly among subjects with low-grade cervical squamous lesions. A significant increase of both HPV types unrelated to nonavalent vaccination and negative/untypable HPV infections was reported. The prevalence of HPV types among subjects with abnormal pap smears in Northern Italy is changing. Many variables including demographic factors and possibly vaccination could be responsible for this modification.

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