Severity Of Cervical Neoplasia Research Articles

Modern Conservative Etiopathogenetic Treatment of Cervical Intraepithelial Neoplasia (literature review)

Annotation. We used PubMed, Cochrane Library, Google Scholar databases, mostly referring to publications from the last five years (2016–2020). The long-term persistence of oncogenic types of human papilloma virus is the main etiological factor for cervical intraepithelial neoplasia (CIN). Prolonged persistence of herpes infection can also have a transformative effect on cervical epithelium. Since this pathology is most often diagnosed in women of reproductive age, the maximum preservation of reproductive function, prevention of perinatal complications requires the search for new conservative CIN treatments aimed at the complete elimination of viruses and neoplastic cells. The effectiveness of conservative antiviral therapy of CIN I, II without the use of surgical methods has been proved, especially in women who have not fulfilled their reproductive plans. In addition, antiviral therapy during pre- and postoperative periods contributes to the reduction of complications and relapses in women with severe cervical neoplasia.

Прогностическое значение экспрессии белков Ki-67 и p16 у беременных женщин, инфицированных ВПЧ, в оценке течения интраэпительных поражений шейки матки

The purpose — to determine the expression of Ki-67 and p16 in pregnant women infected with HPV, and their role in the diagnosis and prognosis of severe cervical neoplasia. Material and methods. Design: open-label observational non-interventional cohort clinical study. We examined 26 pregnant women infected with HPV, aged 23 to 31 years. Methods: general clinical nethods, Kvant-21 test for determining HPV types and quantitative load, cytological examination, determination of the expression of Ki-67 and p16 proteins by immunocytochemical method. Results. It was shown that with an increase of the cervical lesion severity, the proportion of patients with tumor markers increased (from 20% with NILM to 100% with HSIL), and the intensity of Ki-67/p16 expression was moderate (2+) in 25% of patients with LSIL and high (3+) in 100% of patients with HSIL. A higher statistically significant viral load was detected for the HPV A9 DNA group (16, 31, 33, 35, 52, 58 types) upon detection of tumor markers compared with their absence, confirmed by a logit regression model with a sensitivity of 100% and a specificity of 89%. Conclusion. Due to the lack of an unambiguous opinion about the extent to which changes in the expression of Ki-67 and p16 reflect information about the CIN evolution during pregnancy, further research is needed to obtain data that would allow for an appropriate interpretation of the revealed phenomena.

Cytokine expression profiles in cervical mucus from patients with cervical cancer and its precursor lesions

Human papillomavirus (HPV) infection can persist in the cervical epithelium without provoking a strong host immune response, leading to the development of cervical cancer. Cytokines, which mediate innate and adaptive immune activities, are secreted in the cervical mucus; however, there is currently no appropriate method for assessing cytokine levels in mucus specimens. Here, we employed multiplexed bead-based immunoassays to examine cytokine levels in cervical mucus using both weighted-volume and total protein concentration methods to adjust for different specimen volumes in individual patients. Out of 18 cytokines initially examined in the primary cohort patient group (n = 28), 14 were detected in more than 10% of the samples. Of these 14 cytokines, expression levels of interferon (IFN)-γ, granulocyte–macrophage colony-stimulating factor (GM-CSF), RANTES, and eotaxin were significantly increased with the disease severity in the secondary cohort patient group (n = 235). We also examined associations between cytokine levels and clinical parameters, such as cytology and HPV genotype. Of the 14 cytokines, granulocyte colony-stimulating factor (G-CSF) was downregulated in HPV-positive specimens. Examination of co-expression patterns of cytokines in relation to HPV infection status revealed that several pairs of cytokines were simultaneously upregulated in HPV-positive cases, including INF-γ and interleukin (IL)-17A, GM-CSF and monocyte chemoattractant protein-1 (MCP-1), GM-CSF and RANTES, IL-17A and RANTES, and MCP-1 and eotaxin. Interestingly, upregulation of GM-CSF and RANTES might reflect a shift in immuno-regulatory cytokines in HPV-positive specimens, potentially associated with more severe cervical neoplasia.

Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women.

Vaginal infections may affect susceptibility to and clearance of human papillomavirus (HPV) infection and chronic inflammation has been linked to carcinogenesis. This study aimed to evaluate the association between bacterial vaginosis (BV) and inflammatory response (IR) with the severity of cervical neoplasia in HPV-infected women. HPV DNA was amplified using PGMY09/11 primers and genotyping was performed using a reverse line blot hybridization assay in 211 cervical samples from women submitted to excision of the transformation zone. The bacterial flora was assessed in Papanicolaou stained smears, and positivity for BV was defined as ≥ 20% of clue cells. Present inflammatory response was defined as ≥ 30 neutrophils per field at 1000× magnification. Age higher than 29 years (OR:1.91 95% CI 1.06-3.45), infections by the types 16 and/or 18 (OR:1.92 95% CI 1.06-3.47), single or multiple infections associated with types 16 and/or 18 (OR: 1.92 CI 95% 1.06-3.47), BV (OR: 3.54 95% CI 1.62-7.73) and IR (OR: 6.33 95% CI 3.06-13.07) were associated with severity of cervical neoplasia (CIN 2 or worse diagnoses), while not smoking showed a protective effect (OR: 0.51 95% CI 0.26-0.98). After controlling for confounding factors, BV(OR: 3.90 95% CI 1.64-9.29) and IR (OR: 6.43 95% CI 2.92-14.15) maintained their association with the severity of cervical neoplasia. Bacterial vaginosis and inflammatory response were independently associated with severity of cervical neoplasia in HPV-positive women, which seems to suggest that the microenvironment would relate to the natural history of cervical neoplasia.

Polarized Light Colposcopy Compared With Standard Colposcopy

The objective of this study was to determine the potential benefits of polarized light colposcopy compared with standard colposcopy examinations in the evaluation of women with abnormal cervical cytology. Polarized and standard colposcopy examinations were performed on 330 subjects. Respective images and biopsy annotations were obtained. Sensitivity and specificity; differences in the severity of cervical neoplasia; agreement of colposcopy impression, biopsy intent, and biopsy site; and differences in the number of biopsies were determined using the ROC, Bowker's test of symmetry, kappa statistic, and paired t test, respectively. The sensitivity and specificity for a lesion being seen with nonpolarized light and polarized light colposcopy were 96.8% and 64.5%, and 96.8% and 64.9%, respectively. There was no statistically significant difference in the ROC of the lesion being seen between nonpolarized (80.7) and polarized (80.9) colposcopy. Likewise, there was no statistically significant difference in the ROC of intent to biopsy between nonpolarized (80.2) and polarized colposcopy (78.8). The agreement of cervical histopathology and colposcopy impression for nonpolarized and polarized colposcopy were 0.986 and 0.952, respectively. There was no significant difference between nonpolarized and polarized colposcopy in the mean number of lesions seen or number of sites intended to biopsy. Polarized light colposcopy was not useful as an adjunct to conventional colposcopy in this study. Further research needs to be performed to determine the overall utility of polarized light colposcopy in clinical practice.

Different DNA methylation pattern of HPV16, HPV18 and HPV51 genomes in asymptomatic HPV infection as compared to cervical neoplasia

Epigenetic alterations of human papillomavirus (HPV) genome play an important role in virus life cycle and carcinogenic progression. The aim of the current study was to investigate the correlation between the grade of cervical pathology and DNA methylation status within the L1 gene and the long control region (LCR) of HPV16, HPV18 and HPV51. HPV genomes were analyzed using bisulfite DNA modification procedure with the subsequent amplification of target DNA regions and sequencing. A collection of 202 cervical specimens was analyzed: 157 HPV16-positive specimens, 21 HPV18-positive specimens and 24 HPV51-positive specimens. This study revealed that methylation of CpG was significantly more prevalent in L1 gene as compared to LCR region of all three studied HPV types and the degree of DNA methylation level correlated with the severity of cervical neoplasia. An increased DNA methylation level of HPV16 promoter region in case of cervical cancer was determined.

Chlamydia trachomatis Co-infection in HPV Positive Women brings no Additional Risk of High-grade Cervical Intraepithelial Neoplasia

Background: Co-infection by Chlamydia trachomatis (CT) in women with Human Papillomavirus (HPV) infection has been shown to increase the risk of developing cervical intraepithelial neoplasia (CIN). The present study was designed to analyze the association between HPV e CT co-infection and the severity of cervical neoplasia. Methods: Two hundred fifty-one women with PCR-confirmed HPV infection were tested for CT co-infection by PCR, prior to cervical conizations due to CIN. Prevalence rates of CT and HPV types were reported for the histological diagnosis categories. Results: The prevalence of Chlamydia trachomatis was 15.1% (38/251). CT negative women showed a significant association between age ≥ 30 years and CIN 2 or worse diagnosis; this association was not found in CT positive women. In women < 29 years of age, negative for CT, the infection by HPV 16 /18 were detected in 50% of the women with CIN 2 or worse diagnosis and in 19.5% of women with CIN 1 or negative (OR=5.83; 95%CI: 2.19-15.57). Conclusion: No association with CIN 2 or worse diagnosis was observed for Chlamydia trachomatis positive women for all age groups. These data can suggest that HPV type and no CT infection may correlate with risk for severity of histological diagnoses in younger women.

Expression of MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2 in Intraepithelial and Invasive Cervical Neoplasia

Aim: To evaluate the expression of MMP-2, MMP-9, MMP-14, TIMP-1 and TIMP-2 in Cervical intraepithelial neoplasia grade 3 (CIN 3) and invasive squamous cell carcinoma. Methods and Results: This study comprised three groups: Group 1: 55 cases with CIN 3; Group 2: 30 cases with CIN 3 and invasive carcinoma components; Group 3: 46 cases with invasive carcinoma. Protein expression was investigated in tumor and stromal cells by immunohistochemistry and percentages of immunostained cells were determined. The mean percentage of MMP-14 tumor cells was significantly higher in stromal cells in all groups. TIMP-2 and MMP-9 expression was significantly higher in stromal cells than in tumor cells. TIMP-1 had a significantly higher expression in stromal cells of carcinoma and tumor cells of CIN 3. Stromal cells expression of MMP-2, MMP- 14, TIMP-1 was increased with the severity of cervical neoplasia. The expression of MMP-2 in stromal cells that was higher in CIN 3 component of Group 2 than in CIN 3 of Group 1. Conclusions: The increase in MMP-2 expression from CIN 3 to invasive cervical cancer reinforces their role in cervical cancer progression. From CIN 3 to invasive cervical carcinoma, TIMP-1 expression increased in stromal cells and decreased in tumor cells.

Association of CDKN2A polymorphisms with the severity of cervical neoplasia in a Brazilian population

Variants of p16(INK4a) and p14(ARF), encoded by the CDKN2A locus, may respond differently to the presence of human papillomavirus (HPV). We investigated the potential association of two CDKN2A polymorphisms, 500C > G (rs11515) and 540C > T (rs3088440), with cervical neoplasia in patients with cervical lesions and healthy controls (n = 492). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single-strand conformation polymorphism (SSCP) and/or DNA sequencing techniques were employed for genotyping. The 500G allele was found higher, whereas the 540T/T genotype was less frequent in patients with more severe lesions. The CDKN2A variants may have the potential to be markers for the management of patients with cervical neoplasia.

Chlamydia trachomatis infection and human papillomavirus in women with cervical neoplasia in Pernambuco-Brazil

Chlamydia trachomatis (CT) is the most common bacterial cause of sexually transmitted disease. High-risk human papillomavirus (HR-HPV) is considered the main etiological agent for cervical neoplasia. Evidences showed that the presence of co-infection of CT and HR-HPV plays a central role in the etiology of cervical intraepithelial neoplasia (CIN) and cervical cancer. The goals of this study were: evaluate the human papillomavirus (HPV) and CT prevalence among Brazilian women with abnormal cytology and provide the effect of this association on the severity of cervical neoplasia. The population of this study was composed by 142 women with incident histological incidence of CIN grades I, II, III or cervical cancer from Recife, Northeast of Brazil. The polymerase chain reaction method on a cervical brush specimen was used to detect both agents and the automatic sequencing method was used for HPV genotyping assay. The prevalence of HPV and CT was 100 and 24.65%, respectively. Thirteen types of HPV were detected; HPV 16, 18, 31 and 33 were the most common. The most prevalent HPV types were HPV 16 and 18. A significant association between CT positive and HPV 16 infection was found (p<0.0106; OR=5.31; 95% IC1.59-17.67). In the study population, there was diversity of HPV infections, with high-risk types being the most common. Also, the data collected suggest that CT infection may play an important role in the natural history of HPV infection.

Immunohistochemical Expression of Cyclin D1, p16Ink4a, p21WAF1, and Ki-67 Correlates With the Severity of Cervical Neoplasia

High-risk human papillomaviruses are closely associated with cervical cancer and its precursor lesions through interactions between the E6 and E7 oncoproteins and the cell-cycle regulatory proteins, such as p53 and pRb, respectively. As other molecules involved in the cell-cycle control seem to be important for human papillomavirus (HPV)-mediated cervical carcinogenesis, we have analyzed the expression of p53, p21, p16, cyclin D1, and Ki-67 and the presence of HPV (HPV pool and HPV-16) by immunohistochemical studies using tissue microarray in low squamous intraepithelial lesions (n=50), high squamous intraepithelial lesions (n=98), and cervical carcinoma (n=18). We have found a significant increase in the expression of p16 and p21 (P<0.001) from low- to high-grade lesions and cancer. In contrast, cyclin D1 expression showed a significant decrease in more severe lesions (P<0.001). p16, Ki-67, p21, and p53 positivity increased with the cell-layer level and the lesion severity, with stronger correlations being observed for p16 and Ki-67. High positivity for HPV pool (96.3%) and HPV-16 (77.5%) immunostaining was detected in all cases, with an association between p16 and cyclin D1 expression and HPV-16 infection. Our tissue microarray results corroborate the usefulness of the immunohistochemical assessment of cell-cycle biomarkers in distinguishing different groups of precursor lesions of the cervix and cervical carcinoma.

Methylation of human papillomavirus-52 and -58 is a candidate biomarker in cervical neoplasia

BackgroundPrevious studies of human papillomavirus (HPV)16/18 genome methylation have concluded that methylation status of the L1 gene might act as a biomarker for cervical intraepithelial neoplasia (CIN). ObjectivesWe investigated the correlation between methylation status in the L1 gene and the long control region (LCR) of HPV52/58 and CIN. Study designExfoliated cervical cells were taken from 54 HPV52-positive and 41 HPV58-positive women. The HPV genome was examined using bisulfite modification, polymerase chain reaction amplification, and sequencing. ResultsThe CpGs were unmethylated or hypomethylated in the HPV52/58 LCR. In contrast, the methylation status of the HPV52 L1 gene was correlated with the severity of cervical neoplasia, with average percentages of 15%, 34%, and 52% for cervicitis/CIN1, CIN2, and CIN3, respectively (P<0.05). Methylation status of the HPV52 L1 gene was also correlated with the prognosis of CIN1/2, with median percentages of 15% and 35% for regression and persistence/progression, respectively (P<0.05). The methylation status of the HPV58 L1 gene was correlated with the severity of cervical neoplasia, with average percentages of 12%, 38%, and 61% for cervicitis/CIN1, CIN2, and CIN3, respectively (P<0.05). ConclusionsThe increased methylation at the CpG sites in the HPV52/58 L1 gene was correlated with the severity of cervical neoplasia, similar to HPV16/18 in previous studies. These data suggest that HPV methylation status of the L1 gene is a candidate biomarker of CIN for detecting CIN2 and CIN3.

Intratypic variants of human papillomavirus type 16 and risk of cervical Neoplasia in Taiwan

The associations between variants of human papillomavirus (HPV) 16 and risk of cervical neoplasia have been reported, but nucleotide variations of HPV 16 in Asian populations and their association with cervical neoplasia have not been evaluated extensively. During 1991-1992, 11,923 women from seven townships in Taiwan were enrolled. The HPV DNA in cervical cells was detected and genotyped using EasyChip HPV blot. Nucleotide variations in the long control region (LCR), E6, and E7 genes were determined using DNA sequencing for 170 HPV 16-positive cervical samples. The Asian variant was the most prevalent variant (81.8%) of HPV 16 in Taiwan, and was also associated with increased prevalence of histologically confirmed cervical intraepithelial neoplasia grade 3 or worse, showing an age-adjusted odds ratio (exact confidence limits) of 10.70 (1.62-451.05; P = 0.0049) compared to the HPV 16 European variant. Similar significant associations with cervical intraepithelial neoplasia grade 3 or worse were also observed for distinct nucleotide substitutions, including T178A/G, A647G, A7730C/G, T7781C, G7842A, and C24T/G. These results demonstrate that non-European variants (non-E) of HPV 16, predominantly Asian variants, are associated with increased risk for severe cervical neoplasia, compared with European variants. Molecular mechanisms accounting for varied cervical neoplasia risk among different HPV 16 variants warrant further investigation.

Association of HPV infection and Chlamydia trachomatis seropositivity in cases of cervical neoplasia in Midwest Brazil

High-risk human papillomavirus (HPV) is considered the main etiological agent for cervical neoplasia. However, the presence of a single type HPV infection alone is unlikely to be sufficient to cause cervical cancer. There is epidemiologic evidence suggesting that HPV and Chlamydia trachomatis play a central role in the etiology of cervical intraepithelial neoplasia and subsequent cervical cancer. To evaluate the HPV prevalence and the seropositivity for C. trachomatis in women referred to the colposcopy clinic due to an abnormal cervical smear and to examine the effect of this association on the severity of cervical neoplasia. Following enrollment, 131 patients underwent colposcopy and biopsies when necessary. HPV DNA was detected by the polymerase chain reaction (PCR) and genotyping was performed by reverse line-blot hybridization assay. C. trachomatis seropositivity was tested by ELISA for the detection of IgG antibodies. The prevalence of HPV infection was 86.3%. Seropositivity for C. trachomatis was 26%. Thirty-one women (27.4%) were positive for C. trachomatis antibodies and HPV-DNA. The most prevalent HPV type in C. trachomatis-seropositive women were HPV 16 (51.6%) and this HPV type was present mainly in neoplasia cases. Positivity for HPV, particularly HPV types 16 and 18, and C. trachomatis seropositivity was significantly associated with a diagnosis of high grade neoplasia. Borderline significance was observed after adjustment for HPV. C. trachomatis seropositivity is associated with high grade neoplasia in women infected with HPV, mainly when the types 16 and 18 were involved.

Promoter hypermethylation of CDH13, DAPK1 and TWIST1 genes in precancerous and cancerous lesions of the uterine cervix

Aberrant DNA methylation is an early event in carcinogenesis and could serve as an additional molecular marker for the early diagnosis. The study was performed to investigate the promoter methylation of DAPK1, CDH13, and TWIST1 genes in uterine cervix lesions in an effort to examine whether this epigenetic event is involved in the process of cervical carcinogenesis, and whether it might be used as a molecular marker of cervical lesions. We conducted a retrospective study of 60 uterine cervix specimens, including 8 normal tissue samples, 10 benign lesions, 28 precancerous lesions (CIN1–3), and 14 squamous cell carcinomas (SCC). DNA hypermethylation was investigated using methylation-specific PCR. Immunohistochemistry was used to find p16 INK4A overexpression. No hypermethylated promoters were detected in normal tissues and benign lesions. However, promoter hypermethylation of CDH13, TWIST1, and DAPK1 increased progressively from CIN1 to cancer, reaching values higher than 50% for cancer. DAPK1 and CDH13 displayed a significantly increased frequency of promoter methylation with progressively more severe cervical neoplasia ( p < 0.05). A statistically significant association was observed between p16 INK4A expression and hypermethylation of DAPK1, TWIST1, and CDH13 ( p < 0.0001). Hypermethylation of CDH13, DAPK1, and TWIST1 promoters is an early event in the initiation and progression of cervix neoplasia. CDH13, DAPK1, and TWIST1 genes are potential biomarkers of cervical cancer risk.

Type‐specific human papillomavirus oncogene messenger RNA levels correlate with the severity of cervical neoplasia

This study aimed to evaluate whether quantitation of high-risk human papillomavirus (HR-HPV) E6 messenger RNA (mRNA) can be a potential biomarker for detecting the severity of cervical lesions. HPV genotyping was performed using a modified MY11/GP6+ PCR for HPV DNA amplification, followed by HPV genotype-specific hybridization with on a gene chip. E6 type-specific PCR was used to validate multiple infections. Quantitative real-time reverse transcriptase (QRT-PCR) and real-time PCR used to measure mRNA levels and DNA viral loads of 6 HPV oncogenic types (HPV 16, 18, 31, 33, 52 and 58) in 720 liquid-based cytology samples. The HPV DNA and RNA measurements were correlated with cervical lesions diagnosed by histopathologic examination. mRNA transcripts in the 6 types HPV DNA-positive cases was lower in normal women and <CIN 1 (23%), women with CIN 1 (54%), CIN2+ (77%) and CIN3+ (80%) (p < 0.001). Geometric mean mRNA levels ranged from 24.5 (copies per 50 ng total RNA) in normal women and <CIN 1 to 210.8 in those with CIN 1, 629.0 in CIN2+ and 699.0 in CIN3+ (p < 0.0001). Trends of increasing viral mRNA with severity of histopathologic diagnosis were significant for HPV 16, 18, 52 and 58 transcripts but not for HPV 31 and 33 transcripts. However, geometric mean DNA viral loads of HPV 16, 18, 52 and 58 DNA did not significantly increase with the severity of cervical dysplasia. Therefore, quantitative HPV E6 mRNA levels of high-risk HPV types are potentially useful biomarkers for distinguishing among HPV infections, cervical precancerous lesions and cancer.

Folate Status and Aberrant DNA Methylation Are Associated With HPV Infection and Cervical Pathogenesis

Aberrant DNA methylation is a recognized feature of human cancers, and folate is directly involved in DNA methylation via one-carbon metabolism. Previous reports also suggest that folate status is associated with the natural history of human papillomavirus (HPV) infection. A cross-sectional study was conducted to test the hypothesis that folate status and aberrant DNA methylation show a progressive change across stages of cervical pathology from normal cells to cervical cancer. Additionally, we postulated that a gene-specific hypermethylation profile might be used as a predictive biomarker of cervical cancer risk. DNA hypermethylation of seven tumor suppressor genes, global DNA hypomethylation, systemic folate status, and HPV status were measured in 308 women with a diagnosis of normal cervix (n = 58), low-grade cervical intraepithelial neoplasia (CIN1; n = 68), high-grade cervical intraepithelial neoplasia (CIN2, n = 56; and CIN3, n = 76), or invasive cervical cancer (ICC; n = 50). Lower folate status was associated with high-risk HPV infection (P = 0.031) and with a diagnosis of cervical intraepithelial neoplasia or invasive cervical cancer (P < 0.05). Global DNA hypomethylation was greater in women with invasive cervical cancer than all other groups (P < 0.05). A cluster of three tumor suppressor genes, CDH1, DAPK, and HIC1, displayed a significantly increased frequency of promoter methylation with progressively more severe cervical neoplasia (P < 0.05). These findings are compatible with a role for folate in modulating the risk of cervical cancer, possibly through an influence over high-risk HPV infection. DAPK, CDH1, and HIC1 genes are potential biomarkers of cervical cancer risk.

Differential viral loads of human papillomavirus 16 and 58 infections in the spectrum of cervical carcinogenesis

Human papillomavirus (HPV) load was reported to be related to the severity of cervical neoplasia but with controversy. The viral load-disease severity relationship was showed in HPV 16, but no study was made in HPV 58, the second most prevalent HPV in cervical cancer in East Asia. We studied cervical HPV loads in HPV 16- and HPV 58-infected cases of normal, low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and invasive cervical cancer (CC) by using quantitative polymerase chain reaction (Q-PCR) with type-specific primers in defined cell number. With the exception of HPV 16 infection in normal, viral loads varied greatly in each disease regardless of genotypes. The load of HPV 16 differed significantly among disease severities, with a dramatic increase from normal (1.14 +/- 2.25 copies/cell) to LSIL, HSIL, and CC (1599 +/- 2301, 7489 +/- 24,087 and 1878 +/- 2979 copies/cell, respectively) (P < 0.01). No significant difference was noted among different HPV 58 infections, with loads in normal, LSIL, HSIL, and CC of 503 +/- 641, 7951 +/- 27,557, 353 +/- 744, and 1139 +/- 2895 copies/cell, respectively. In comparison with HPV 16, HPV 58 subclinical infection confers a significant higher load (P < 0.01). Different HPV types behave differentially in the spectrum of cervical carcinogenesis. Unlike HPV 16, the infection load of HPV 58 does not correlate to the clinical severity. The wide variation of HPV loads among different HPV types and among squamous intraepithelial lesions and CC makes the viral load test unrealistic in differentiating different severities of cervical neoplasia.

Detection of Cancer-Related Gene Expression Profiles in Severe Cervical Neoplasia

Detection of Cancer-Related Gene Expression Profiles in Severe Cervical Neoplasia

Chlamydia trachomatis, herpes simplex virus 2, and human T-cell lymphotrophic virus type 1 are not associated with grade of cervical neoplasia in Jamaican colposcopy patients.

A few recent studies have suggested that other sexually transmitted infections may increase the likelihood of a human papillomavirus (HPV) infection progressing to high-grade cervical neoplasia and cancer. The goal was to assess whether exposures to Chlamydia trachomatis, human T-cell lymphotrophic virus type 1 (HTLV-I), and/or human simplex virus type 2 (HSV-2) are greater in colposcopy patients with cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) than in patients with low-grade cervical neoplasia (CIN1). Sequential patients (n=447) attending a colposcopy clinic in Kingston, Jamaica, a country with high cervical cancer rates and high HTLV-I prevalence, were tested for (1) HPV DNA by L1 consensus primer (MY09/11) polymerase chain reaction assays, (2) C trachomatis DNA by ligase chain reaction, (3) C trachomatis antibodies by both microimmunofluorescence and a peptide (VS4) enzyme linked immunosorbent assay (ELISA), (4) HTLV-I antibodies by ELISA confirmed by western blotting, and (5) HSV-2 antibodies by a recombinant HSV-2-specific ELISA. Odds ratios and 95% confidence intervals were estimated with use of multinomial logistic regression models. HPV DNA detection was associated with grade of cervical neoplasia but other evaluated sexually transmitted infections were not. HTLV-I, C trachomatis, and/or HSV-2 were not associated with severity of cervical neoplasia in Jamaican women.