The utility of high-risk HPV testing in the management of women 30 to 64 years of age with low-grade squamous intraepithelial lesions on cervical cytology

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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Prediction of clinical outcome using p16INK4a immunocytochemical expression in low-grade squamous intraepithelial lesions and high-risk HPV-positive atypical squamous cells of undetermined significance in patients with and without colposcopic evident cervical disease

Experimental and Therapeutic Medicine ◽

10.3892/etm.2011.316 ◽

2011 ◽

Vol 2 (5) ◽

pp. 853-858 ◽

Cited By ~ 3

Author(s):

ANKICA LUKIC ◽

GIORGIO SBENAGLIA ◽

ELISABETTA CARICO ◽

MATILDE DI PROPERZIO ◽

ENRICO GIARNIERI ◽

...

Keyword(s):

High Risk ◽

Clinical Outcome ◽

Low Grade ◽

Squamous Intraepithelial Lesions ◽

Squamous Cells ◽

Cervical Disease ◽

High Risk Hpv ◽

Intraepithelial Lesions ◽

Undetermined Significance

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The Effect of Local Photodynamic Therapy for 5-aminolevulinic acid in the Treatment of Cervical Low-grade Squamous Intraepithelial Lesions with High-Risk HPV Infection: A Retrospective Study

Photodiagnosis and Photodynamic Therapy ◽

10.1016/j.pdpdt.2020.102172 ◽

2021 ◽

pp. 102172

Author(s):

Liying Gu ◽

Mengxing Cheng ◽

Zubei Hong ◽

Wen Di ◽

Lihua Qiu

Keyword(s):

Photodynamic Therapy ◽

Retrospective Study ◽

High Risk ◽

Aminolevulinic Acid ◽

Hpv Infection ◽

Low Grade ◽

Squamous Intraepithelial Lesions ◽

High Risk Hpv ◽

Intraepithelial Lesions

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Detection of antibodies against a human papillomavirus (HPV) type 16 peptide that differentiate high-risk from low-risk HPV-associated low-grade squamous intraepithelial lesions

Journal of General Virology ◽

10.1099/vir.0.80077-0 ◽

2004 ◽

Vol 85 (9) ◽

pp. 2643-2650 ◽

Cited By ~ 14

Author(s):

Leticia Rocha-Zavaleta ◽

Juana P. Ambrosio ◽

Maria de Lourdes Mora-Garcia ◽

Fernando Cruz-Talonia ◽

Jorge Hernandez-Montes ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Cancer Patients ◽

Low Risk ◽

Low Grade ◽

Squamous Intraepithelial Lesions ◽

Hpv Dna ◽

Iga Antibodies ◽

High Risk Hpv ◽

Intraepithelial Lesions

A nonapeptide (16L1) was derived from the human papillomavirus type 16 (HPV-16) major capsid protein and tested for detection of potential cross-reactive serum IgG and cervical IgA antibodies in low- and high-risk HPV-associated low-grade squamous intraepithelial lesions (LSIL) and cervical cancer patients by ELISA. The IgG response was similar in women with low-risk HPV-associated LSIL and controls (P=0·1). In contrast, more than 90 % of patients with high-risk HPV-associated LSIL were seropositive. Although tumours from cancer patients were all positive for the presence of high-risk HPV DNA, the level of seropositivity decreased significantly in this group (P<0·0001). Cervical IgA antibodies were also detected in a significantly high proportion of women with high-risk HPV-associated LSIL compared with controls. However, the proportion of IgA-positive patients was lower than the proportion of IgG seropositives. In conclusion, the 16L1 peptide appears to be a high-risk type-common epitope that induces cross-reactive antibodies in high-risk, but not low-risk, HPV-associated LSIL patients, allowing differentiation of high- and low-risk infected women at this stage of infection.

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Association of human papillomavirus and bacterial vaginosis with increased risk of high-grade squamous intraepithelial cervical lesions

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2018-000076 ◽

2019 ◽

Vol 29 (2) ◽

pp. 242-249 ◽

Cited By ~ 6

Author(s):

Tamy Tiemi Suehiro ◽

Natália Malaguti ◽

Edilson Damke ◽

Nelson Shozo Uchimura ◽

Fabrícia Gimenes ◽

...

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Bacterial Vaginosis ◽

Low Grade ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Hpv Dna ◽

Increased Risk ◽

High Risk Hpv ◽

Intraepithelial Lesions

ObjectiveTo assess the rates of co-infections between human papillomavirus (HPV) and 13 key markers of bacterial vaginosis in cervical samples by multiplex polymerase chain reaction in a population with a high rate of abnormal cytology and a positive HPV test.MethodsThe study included a total of 213 women aged 18–72 years screened using Papanicolaou smears for determining cervical abnormalities and for HPV and bacterial vaginosis by single-target and multiplex polymerase chain reaction.ResultsA total of 83 (39%) women were negative for intraepithelial lesion or malignancy cytology and 130 (61%) had abnormal cytology. HPV-DNA prevalence was 69.9% and bacterial vaginosis was 72.7 %. Co-infections between bacterial vaginosis with HPV-DNA and high-risk HPV were associated with an increased risk for squamous intraepithelial lesions of low-grade cytology and high-grade squamous intraepithelial lesions plus cervical cancer. The most frequent bacterial vaginosis agent was Gardnerella vaginalis (33.8%), and co-infection with HPV-DNA and high-risk HPV increased the risk for squamous intraepithelial lesions of low grade cytology and high-grade squamous intraepithelial lesions plus cervical cancer. Co-infection between Megasphaera type I and high-risk HPV increased the risk for high-grade squamous intraepithelial lesions plus cervical cancer.ConclusionsOur results reinforce the hypothesis that some bacterial vaginosis agents may play a role as co-factors in HPV-mediated cervical carcinogenesis, at least in some populations.

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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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The effectiveness of acetic acid wash protocol and the interpretation patterns of blood contaminated cervical cytology ThinPrep® specimens

CytoJournal ◽

10.4103/1742-6413.168060 ◽

2015 ◽

Vol 12 ◽

pp. 23 ◽

Cited By ~ 2

Author(s):

Nora K. Frisch ◽

Yasin Ahmed ◽

Seema Sethi ◽

Daniel Neill ◽

Tatyana Kalinicheva ◽

...

Keyword(s):

Acetic Acid ◽

Statistical Significance ◽

Cervical Cytology ◽

Low Grade ◽

Squamous Intraepithelial Lesions ◽

Chi Square ◽

Chi Square Test ◽

Acid Wash ◽

The Difference ◽

Intraepithelial Lesions

Background: ThinPrep® (TP) cervical cytology, as a liquid-based method, has many benefits but also a relatively high unsatisfactory rate due to debris/lubricant contamination and the presence of blood. These contaminants clog the TP filter and prevent the deposition of adequate diagnostic cells on the slide. An acetic acid wash (AAW) protocol is often used to lyse red blood cells, before preparing the TP slides. Design: From 23,291 TP cervical cytology specimens over a 4-month period, 2739 underwent AAW protocol due to initial unsatisfactory smear (UNS) with scant cellularity due to blood or being grossly bloody. Randomly selected 2739 cervical cytology specimens which did not undergo AAW from the same time period formed the control (non-AAW) group. Cytopathologic interpretations of AAW and non-AAW groups were compared using the Chi-square test. Results: About 94.2% of the 2739 cases which underwent AAW were subsequently satisfactory for evaluation with interpretations of atypical squamous cells of undetermined significance (ASCUS) 4.9% (135), low-grade squamous intraepithelial lesions (LSIL) 3.7% (102), and high-grade squamous intraepithelial lesions (HSIL) 1% (28). From the 2739 control cases, 96.3% were satisfactory with ASCUS 5.5% (151), LSIL 5.1% (139), and HSIL 0.7% (19). The prevalence of ASCUS interpretations was similar (P = 0.33). Although there were 32% more HSIL interpretations in the AAW group (28 in AAW vs. 19 in non-AAW), the difference was statistically insignificant (P = 0.18). AAW category; however, had significantly fewer LSIL interpretations (P = 0.02). The percentage of UNS cases remained higher in the AAW group with statistical significance (P < 0.01). Conclusions: While AAW had a significantly higher percent of UNS interpretations, the protocol was effective in rescuing 94.2% of specimens which otherwise may have been reported unsatisfactory. This improved patient care by avoiding a repeat test. The prevalence of ASCUS and HSIL interpretations between AAW and non-AAW groups were comparable. Though not statistically significant, HSIL interpretations were relatively higher in the AAW group. LSIL interpretations showed lower prevalence in AAW group.

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