Human Papillomavirus 16-Associated Cervical Intraepithelial Neoplasia in Humans Excludes CD8 T Cells from Dysplastic Epithelium

This study evaluated the detection of human papillomavirus (HPV) 16 antibody in HPV 16–associated cervical intraepithelial neoplasia (CIN) in Australian women. Seroreactivity to HPV 16 L1 virus–like particles was assessed in patients with CIN 2 (n = 169) and CIN 3 (n = 229) lesions previously tested for the presence of HPV DNA. Seropositivity was significantly commoner in women with HPV 16 DNA–positive lesions (98/184) than in women with no HPV DNA in the lesion (15/47) or with HPV of types other than 16 in the lesion (43/167) (P = 0.0004). In addition, seropositivity was observed in 33% (55/169) of women with CIN 2 and 46% (106/229) of women with CIN 3, in keeping with the lower fraction of CIN 2 (57/169) than CIN 3 (127/229) biopsies positive for HPV 16 DNA. HPV 16 seropositivity is most common in women with HPV 16–associated CIN, but many patients with HPV-associated CIN 3 are seronegative, and HPV 16 seropositivity is common in women with CIN associated with other HPV types. Overall, HPV 16 serology is a poor predictor of presence of HPV 16–associated CIN 3 in patient population studied.

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Clinical and immunological rationale for comprehensive approach to prevention and treatment of cervical intraepithelial neoplasia associated with human papillomavirus

Voprosy ginekologii akušerstva i perinatologii ◽

10.20953/1726-1678-2021-3-161-168 ◽

2021 ◽

Vol 20 (3) ◽

pp. 161-168

Author(s):

A.I. Davydov ◽

◽

D.V. Isakov ◽

R.А. Chilova ◽

V.A. Lebedev ◽

...

Keyword(s):

T Cells ◽

Human Papillomavirus ◽

Cervical Intraepithelial Neoplasia ◽

Antiviral Agent ◽

Intraepithelial Neoplasia ◽

Inosine Pranobex ◽

Trained Immunity ◽

Adaptive Immune Cells ◽

Infected Cells ◽

E6 And E7

A clinical and immunological analysis of the use of antiviral agent Inosine Pranobex (IP) as postoperative drug therapy in patients with cervical intraepithelial neoplasia (CIN) associated with human papillomavirus (HPV) is performed. It is known that IP has a high anti-relapse activity adapted to the mechanisms of HPV elimination (through the sequence of oncoproteins E5, E6 and E7, a decrease in the synthesis of interferons (IFNs) occurs and resistance of HPV-infected cells to IFN is formed). In this work, a number of statements justifying the priority of IP in the treatment of patients with CIN associated with HPV is covered, namely that IP induces trained immunity, differentiation of the Th1 subset of CD4+ T cells and proliferation of CD8+ T cells. Conclusion. Inosine Pranobex should be considered as the medication of choice for postoperative monotherapy in patients with HPV-associated CIN. Inosine Pranobex is characterized by mechanisms of action in both virus-infected cells and through the activation of innate and adaptive immune cells. Key words: CIN, human papillomavirus, inosine pranobex, clinical and immunological aspects, trained immunity

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Prediction of Human Papillomavirus 16 E6 Gene Expression and Cervical Intraepithelial Neoplasia Progression by Methylation Status

International Journal of Gynecological Cancer ◽

10.1111/igc.0b013e31819d8a5c ◽

2009 ◽

Vol 19 (3) ◽

pp. 321-325 ◽

Cited By ~ 30

Author(s):

Pavla Hublarova ◽

Roman Hrstka ◽

Pavla Rotterova ◽

Leopold Rotter ◽

Marie Coupkova ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Cervical Intraepithelial Neoplasia ◽

Methylation Status ◽

Gene Promoter ◽

Intraepithelial Neoplasia ◽

Hpv 16 ◽

Human Papillomavirus 16 ◽

E6 Gene ◽

Asymptomatic Women

Introduction:Human papillomavirus (HPV) infection represents the most important risk factor for the development of cervical intraepithelial neoplasia (CIN) and cervical cancer. We aimed to analyze the consequences of methylation of the E6 gene promoter in distinct stages of HPV-16-induced cellular transformation to assess its importance for disease progression.Methods:Human papillomavirus 16 was detected by sensitive polymerase chain reaction (PCR). Determination of E6 gene promoter methylation was analyzed by digestion with specific restriction endonuclease McrBC followed by PCR amplification. Expression of the E6 gene was determined by quantitative real-time PCR.Results:Of 103 cervical smears from asymptomatic women with no cytological and colposcopic abnormalities, 20.4% were HPV-16-positive. Human papillomavirus 16 was present in 44.4% of 18 patients with CIN I, in 62.2% of 143 patients with CIN II/III, and in 74.2% of 31 cervix carcinoma specimens. The incidence of HPV-16 in all lesions compared with asymptomatic women was statistically significant (P< 0.001, Pearsonχ2test). Methylation was detected in 81% (n = 21) of HPV-16-positive asymptomatic smears compared with 62.5% in CIN I (n = 8), 31.5% (n = 89) in CIN II/III, and 43.4% (n = 23) in carcinomas; a statistical significance between lesions and healthy women was found (P< 0.001, Pearsonχ2test). Expression of E6 mRNA correlated with methylation status (P= 0.010, Mann-WhitneyUtest).Conclusions:We conclude that methylation of the E6 gene promoter in HPV-16 genome is a predictive biomarker for cervical cancer progression by regulating the expression of the E6 oncogene.

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