Cervical Local Immune Response for High-Risk Human Papillomavirus Infection

Purpose: To evaluate cervical mucus secretory leukocyte protease inhibitor (SLPI) concentrations in patients with high-risk human papillomavirus (hrHPV) 16 or 18 positive and low-grade squamous intraepithelial lesions (LGSIL) or high-grade squamous intraepithelial lesions (HGSIL). Method: Patients with HPV 16 or 18 positive from 30 to 45 years of age whose cervical cancer screening results reported cytologically LGSIL or HGSIL were included in the study. In the control group, we included participants in the same age with cytology negative and HPV-negative healthy women. All cytological LGSIL or HGSIL results were histopathologically confirmed with colposcopic biopsy specimens. Finally, the study consisted of a total of 3 groups each containing 25 participants as follows: (1) Pap smear and HPV-negative control group, (2) HPV 16 or HPV 18 and LGSIL-positive participants, and (3) HPV 16 or 18 and HGSIL-positive participants. Cervical mucus SLPI levels were analyzed using the enzyme-linked immunosorbent assay method. Results: The mean cervical mucus SLPI levels were 32.94 ng/mL (range: 23-41.29 ng/mL) in the hrHPV + LGSIL group, 29.40 ng/mL (range: 21.03-38.95 ng/mL) in the hrHPV + HGSIL, and 18.75 ng/mL (range: 13.58-29.24 ng/mL) in the healthy control group. Cervical mucus SLPI levels were found to be significantly higher in the hrHPV + LGSIL and hrHPV + HGSIL groups compared to the control group ( P < .001). Conclusions: The data from the present study indicate that SLPI seems to be one of the important immunomodulatory proteins that provide local immune response in cervical mucosa.

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Human papillomavirus–specific viral types are common in Mexican women affected by cervical lesions

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200605000-00015 ◽

2006 ◽

Vol 16 (3) ◽

pp. 1041-1047

Author(s):

P. Piña-Sánchez ◽

D. M. Hernández-Hernández ◽

R. LÓPEZ-ROMERO ◽

G. VÁZQUEZ-ORTÍZ ◽

C. PÉREZ-PLASENCIA ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Low Grade ◽

Squamous Intraepithelial Lesions ◽

Cervical Lesions ◽

Hpv 16 ◽

Female Population ◽

Hpv Types ◽

Intraepithelial Lesions ◽

Hpv 18

Cervical cancer (CC) is the most common in Mexican female population. The human papillomavirus (HPV) 16 and 18 frequencies in worldwide may be different due to geographical distribution. We analyzed the prevalence of HPV types and determinated their association in cervical lesion in a Mexican population. One hundred fifty-nine normal cervical smears, 95 low-grade squamous intraepithelial lesions (LGSIL), 59 high-grade squamous intraepithelial lesions (HGSIL), and 108 CC samples of the patients were collected. HPV types were determined by sequencing. We detected 11 high-risk types, four low-risk types, three not determinated, and two probably high risk. HPV were present in 12%, 57%, 88%, and 92% from normal, LGSIL, HGSIL, and CC samples, respectively. HPV 16 was the most common in all cervical lesions (71.6% in CC). HPV 58 was present in 18.6% of HGSIL, and the HPV 18 in 4.6% of CC. The 76% of all detected viruses belong to A9 species branch. Control women showed high percentage of HPV high-risk infection, suggesting that this is a high-risk group. High frequency of HPV 16 compared with a low incidence of HPV 18 was observed. HPV 58 is frequently detected in HGSIL but low frequency is found in CC. These findings might be considered for HPV screening.

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Genotype-specific human papillomavirus detection in cervical smears.

Acta Biochimica Polonica ◽

10.18388/abp.2008_3028 ◽

2008 ◽

Vol 55 (4) ◽

pp. 687-692 ◽

Cited By ~ 5

Author(s):

Slawa Szostek ◽

Malgorzata Klimek ◽

Barbara Zawilinska ◽

Magdalena Kosz-Vnenchak

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Cervical Carcinoma ◽

Control Group ◽

Squamous Intraepithelial Lesions ◽

Hpv 16 ◽

Hpv Dna ◽

Cervical Smears ◽

Hpv Types ◽

Intraepithelial Lesions

Human papillomavirus (HPV) is widely accepted as a causative agent of cervical cancer. The distribution and prevalence of HPV types depend on geographic region and demographic factors. The aim of this study was to investigate the relationship between the presence of various HPV types and the outcome of cytological examination. Cervical smears were obtained from 125 women from southern Poland: low grade squamous intraepithelial lesions (LSIL) - 44, high grade squamous intraepithelial lesions (HSIL) - 12, cervical carcinoma - 27 and 42 women without abnormality in cytology as a control group. DNA was extracted from the smears and broad-spectrum HPV DNA amplification and genotyping was performed with the SPF 10 primer set and reverse hybridisation line probe assay (INNO-LiPA HPV Genotyping, Innogenetics). HPV DNA was detected in approximately 72% cases, more frequently in women with squamous intraepithelial lesions and cervical carcinoma than in the control group (P < 0.0005). The most frequent type found was HPV 16 (37%), followed by HPV 51 (28%) and HPV 52 (17%). A single HPV type was detected in 51% positive cases, more frequently in cervical cancer specimens. Multiple HPV infection was dominant in women with LSIL and normal cytology. Prevalence of HPV 16 increased with the severity of cervical smear abnormality. For women HPV 16 positive, the relative risk (odds ratio) of the occurrence of HSIL and cervical cancer versus LSIL was 14.4 (95% CI, 3.0-69.2; P=0.001) and 49.4 (95% CI, 6.5-372.8; P < 0.001), respectively. Genotyping of HPV will allow better classification of women with cervical abnormalities into different risk groups and could be useful in therapy.

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PECULIARITIES OF PAPILLOMAVIRUS GENOTYPING IN PATIENTS WITH CERVICAL INTRAEPITHELIAL NEOPLASIA

Ulyanovsk Medico-biological Journal ◽

10.34014/2227-1848-2020-3-104-111 ◽

2020 ◽

pp. 104-111

Author(s):

N.A. Shmakova ◽

G.N. Chistyakova ◽

I.N. Kononova ◽

I.I. Remizova

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

Viral Load ◽

Cervical Intraepithelial Neoplasia ◽

Intraepithelial Neoplasia ◽

Squamous Intraepithelial Lesions ◽

Hpv 16 ◽

The World ◽

Intraepithelial Lesions ◽

Hpv 18

Recently, there has been a steady growth of cervical cancer all over the world, especially in Russia. Patients with cervical cancer have become much younger. At the same time, the human papillomavirus is not only the main factor in the neoplastic process, but it is also one of the most common sexually transmitted infections in the world. The aim of the paper is to assess the prevalence and characteristics of human papillomavirus genotypes in patients with cervical intraepithelial neoplasia. Materials and Methods. During the periodic screening we examined 213 women of a reproductive age with HPV infection. All patients underwent liquid-based cytology and human papillomavirus genotyping by polymerase chain reaction. Results. We revealed that the prevalence of cervical intraepithelial neoplasia among women with papillomavirus infection was 80.3 % (n=171). According to human papillomavirus genotyping, HPV 16 (38 %) and HPV 33 (32 %) prevailed. We also observed positive high correlation between high-grade squamous intraepithelial lesions (HSIL) and HPV 18 (r=+0.759, p=0.001), a negative mean correlation between HPV 45 and low-grade squamous intraepithelial lesions (LSIL) (r=-0.643, p=0.002). A cohort of patients with severe intraepithelial cervical lesions demonstrated high viral load rates. Conclusion. According to the results obtained, we established the dominance of HPV 16 and HPV 33 genotypes in cervical intraepithelial neoplasia. There were significant differences between HSIL and LSIL patients with HPV 18 and HPV 45. There was also a correlation between an increase in the viral load with the severity of the pathological process. Keywords: human papillomavirus, intraepithelial cervical neoplasms, cervical cancer. В последние годы в мире, особенно в России, наблюдается неуклонный рост и «омолаживание» рака шейки матки. При этом вирус папилломы человека является не только основным фактором прогрессирования неопластического процесса, но и одной из наиболее распространенных инфекций, предаваемых половым путем, в мире. Цель. Оценить распространенность и характеристику генотипов папилломавирусной инфекции у пациенток с цервикальными интраэпителиальными неоплазиями. Материалы и методы. Проведено обследование 213 пациенток репродуктивного возраста с ВПЧ-инфекцией, пришедших на профилактический осмотр. Всем женщинам было выполнено цитологическое исследование жидкостным методом и генотипирование вируса папилломы человека методом полимеразной цепной реакции. Результаты. Распространенность цервикальных интраэпителиальных неоплазий среди женщин с папилломавирусной инфекцией составила 80,3 % (171 пациентка). Согласно данным генотипирования вируса папилломы человека превалировал 16-й (38 %) и 33-й типы (32 %). Выявлена положительная высокая корреляционная связь между цервикальными неоплазиями высокой степени онкогенного риска (HSIL) и 18-м типом ВПЧ-инфекции (r=+0,759 при р=0,001), отрицательная средняя корреляционная связь 45-го типа ВПЧ с низкой степенью онкогенного риска (LSIL) (r=-0,643 при р=0,002). Продемонстрированы высокие показатели вирусной нагрузки в когорте пациенток с тяжелыми внутриэпителиальными цервикальными поражениями. Выводы. По результатам полученных данных установлено доминирование 16-го и 33-го генотипов ВПЧ при цервикальных интраэпителиальных неоплазиях с наличием значимых различий между пациентами с HSIL и LSIL в отношении 18-го и 45-го типов, а также связь роста уровня вирусной нагрузки с увеличением степени тяжести патологического процесса. Ключевые слова: вирус папилломы человека, интраэпителиальные новообразования шейки матки, рак шейки матки.

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Prognostic markers of high-grade squamous intraepithelial lesions: the role of p16INK4aand high-risk human papillomavirus

Acta Obstetricia Et Gynecologica Scandinavica ◽

10.1080/00016340601089727 ◽

2007 ◽

Vol 86 (1) ◽

pp. 94-98 ◽

Cited By ~ 19

Author(s):

José Eleutério Jr ◽

Paulo César Giraldo ◽

Ana Katherine Gonçalves ◽

Diane Isabelle Magno Cavalcante ◽

Francisco Valdeci de Almeida Ferreira ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Prognostic Markers ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Intraepithelial Lesions

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Colposcopy, cervical cytology and human papillomavirus detection as screening tools for cervical cancer

Eastern Mediterranean Health Journal ◽

10.26719/2001.7.1-2.100 ◽

2001 ◽

Vol 7 (1-2) ◽

pp. 100-105

Author(s):

Al Alwan Al Alwan

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Pap Test ◽

Screening Tools ◽

Low Grade ◽

Squamous Intraepithelial Lesions ◽

Sampling Device ◽

Squamous Cells ◽

The Bethesda System ◽

Intraepithelial Lesions

A cohort of 77 women referred for routine screening or investigation of Pap test abnormality underwent colposcopic examination. Pap-stained liquid-based preparations were diagnosed and categorized according to the Bethesda system. Residual material on the sampling device was used to detect high-risk oncogenic human papillomavirus DNA. Although the colposcopic failure rate was higher than that of cytology, no lesion was missed when both methods were used together. High-risk types were recorded in 24% of patients with atypical squamous cells of undetermined significance, 45% with low-grade squamous intraepithelial lesions and 79% with high-grade squamous intraepithelial lesions-indicating that the efficacy of cytological screening can be improved by papillomavirus detection.

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Cervical Microbiome and Response to a Human Papillomavirus Therapeutic Vaccine for Treating High-Grade Cervical Squamous Intraepithelial Lesion

Integrative Cancer Therapies ◽

10.1177/1534735419893063 ◽

2019 ◽

Vol 18 ◽

pp. 153473541989306 ◽

Cited By ~ 1

Author(s):

Rahul Ravilla ◽

Hannah N. Coleman ◽

Cheryl-Emiliane Chow ◽

Luisa Chan ◽

Barbara J. Fuhrman ◽

...

Keyword(s):

Human Papillomavirus ◽

Phase I ◽

Therapeutic Vaccine ◽

High Grade ◽

T Helper ◽

Squamous Intraepithelial Lesions ◽

Hpv 16 ◽

Intraepithelial Lesions ◽

Helper Type

Human papillomavirus (HPV) infection is associated with the vast majority of cervical cancer cases as well as with other anogenital cancers. PepCan is an investigational HPV therapeutic vaccine for treating cervical high-grade squamous intraepithelial lesions. The present study was performed to test whether the cervical microbiome influences vaccine responses and to explore host factors as determinants of the cervical microbiome composition in women with biopsy-proven high-grade squamous intraepithelial lesions. In a recently completed Phase I clinical trial of PepCan, histological response rate of 45% (14 of 31 patients), a significant increase in circulating T-helper type 1 cells, and a significant decrease in HPV 16 viral load were reported. DNA, extracted from liquid cytology specimens collected before and after vaccinations, were amplified and then hybridized to a G4 PhyloChip assay to characterize the microbiome. We describe trends that certain bacterial taxa in the cervix may be enriched in non-responders in comparison to responders ( Padj = .052 for phylum Caldithrix and Padj = .059 for phylum Nitrospirae). There was no difference in bacterial diversity between the 2 groups. A permutational analysis of variance performed for various demographic and immune parameters showed significant clustering with microbiome beta diversity for race, HPV 16 status, peripheral T-helper type 1 cells, and HLA-B40 ( P = .001, .014, .037, and .024, respectively). Further analyses showed significant differences at the empirical Operational Taxonomic Unit level for race and HPV 16 status. As these results are from a small Phase I study, further studies are needed to examine the role of cervical microbiome in response to HPV therapeutic vaccines.

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Regulation of cell cycles is of key importance in human papillomavirus (HPV)-associated cervical carcinogenesis

Sao Paulo Medical Journal ◽

10.1590/s1516-31802003000300009 ◽

2003 ◽

Vol 121 (3) ◽

pp. 128-132 ◽

Cited By ~ 17

Author(s):

Sylvia Michelina Fernandes Brenna ◽

Kari Juhani Syrjänen

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Human Papillomavirus ◽

High Risk ◽

Cell Cycle Checkpoints ◽

Low Grade ◽

Clinical Progression ◽

Squamous Intraepithelial Lesions ◽

High Risk Hpv ◽

Intraepithelial Lesions

The rapid progress in molecular biology has allowed the identification of the genes involved in different functions of normal cells and has also improved our understanding of the mechanisms of human carcinogenesis. The human papillomavirus (HPV) is a small double-stranded DNA tumor virus and its genes can manipulate cell cycle control to promote viral persistence and replication. The E6 and E7 proteins of high-risk HPV bind to cell cycle regulatory proteins and interfere with both G1/S and G2/M cell cycle checkpoints much more effectively than the low-risk HPV. The difference between the ability of low and high-risk HPV types to induce immortalization and transformation may well lie in their abilities to interact with the various cell cycle components, resulting in the loss of multiple cell cycle checkpoints, which are important in host genome fidelity, thus potentially resulting in accumulation of genetic abnormalities. Cervical cancer is one of the leading malignancies in women worldwide, with substantial morbidity and mortality. According to current concepts, HPV is recognized as the single most important causal agent in the pathogenesis of this cancer. HPV infection clearly precedes the development of malignancy, while being regularly associated with cervical cancer precursor lesions (all grades of squamous intraepithelial lesions). HPV-infected low-grade squamous intraepithelial lesion (SIL) has three possible outcomes: a) it may regress; b) it can persist; or c) it can make a clinical progression to in situ or invasive carcinoma. It has been well established by prospective cohort studies that the spontaneous regression rate increases in parallel with follow-up duration. In contrast, the clinical progression of lesions usually takes place quite rapidly, i.e. during the first two years from diagnosis. The mechanisms responsible for this divergent clinical behavior of HPV-associated squamous intraepithelial lesions are largely unknown, but currently under intense study in different laboratories worldwide.

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