Incidence Of High-grade Lesions Research Articles

Prevalence of high-risk viral genotypes according to vaccination coverage by the quadrivalent and new nive valent HPV vaccines, and their association and impact on the risk of high-grade lesions

Background The new nine-valent human papillomavirus (HPV) vaccines includes the four HPV genotypes (6, 11, 16 and 18) targeted by the quadrivalent HPV vaccine, plus five additional oncogenic types (31, 33, 45, 52, and 58), and potentially increases the overall prevention of cervical cancer. Objective To determine the prevalence of high-risk viral genotypes according to the protection offered by the actual HPV vaccines, and their association and potential impact on the incidence of high-grade lesions. Methods Cross-sectional study. A total of 595 consecutive women in whom HPV infection had been detected in a cervical smear during routine gynaecological health checks were included. Smear results were classified using the Bethesda system. HPV genotyping was performed using Linear Array HPV genotyping test and they were classified according to the International Agency for Research on Cancer assessment of the carcinogenicity of different HPV types. Odds ratios (OR) with their 95% confidence intervals (95% CI) were estimated by logistic regression, adjusting for age and immigrant status. Prevented fraction among the exposed (PFe-adjusted) was determined as a measure of impact. Results At least one of the additional five high-risk HPV genotypes present in the nine-valent HPV vaccine was detected in 37.66% of women. After excluding women with genotype 16 and/or 18 co-infection, high-risk genotypes (31, 33, 45, 52, 58) were associated with a higher risk of intraepithelial lesion or malignancy: adjusted OR: 3.51 (95% CI: 1.29–9.56), PFe-adjusted 0.72 (95% CI: 0.22–0.90). Genotypes that are still non-vaccine-targeted were detected in 17.98% of women, and non-significantly associated with high-risk lesions. Conclusion The greater protection of the nine-valent HPV vaccine is likely to have impact, because in the absence of genotype 16 or 18 infection, these five genotypes on their own would multiply the risk of a high-grade lesion by 3.5-fold and would be responsible for 72% of high-grade lesions.

Prevalence of high-risk HPV genotypes, categorised by their quadrivalent and nine-valent HPV vaccination coverage, and the genotype association with high-grade lesions

BackgroundThe new nine-valent vaccine against human papillomavirus (HPV) includes the four HPV genotypes (6, 11, 16, and 18) that are targeted by the older quadrivalent HPV vaccine, plus five additional oncogenic types (31, 33, 45, 52, and 58) remain significantly associated with high grade lesions. We aimed to determine the prevalence of high-risk HPV genotypes in unvaccinated subjects and the association of these genotypes with the incidence of high-grade lesions. We also assessed which, if either, of these two HPV vaccines could have prevented these cases.MethodsThis cross-sectional study, conducted from 4 January 2010 to 30 December 2011, was composed of 595 women attending the Hospital General Universitario de Elche (Spain) gynaecology department who were positively screened for opportunistic cervical cancer by pap smears and HPV detection during a routine gynaecological health check. The pap smear results were classified using the Bethesda system. HPV genotyping was performed with the Linear Array HPV genotyping test, and viruses were classified by the International Agency for Research on Cancer assessment of HPV carcinogenicity. Odds ratios (ORs) with their 95% confidence intervals (95% CI) were estimated by logistic regression, adjusting for age and immigrant status. The prevented fraction among those exposed (PFe-adjusted) was determined as a measure of impact.ResultsAt least one of the additional five high-risk HPV genotypes present in the nine-valent HPV vaccine was detected in 20.5% of subjects. After excluding women with genotype 16 and/or 18 co-infection, high-risk genotypes (31, 33, 45, 52, and 58) were associated with a higher risk of intraepithelial lesion or malignancy: adjusted OR = 3.51 (95% CI, 1.29–9.56), PFe-adjusted = 0.72 (95% CI, 0.22–0.90). Genotypes that are still non-vaccine-targeted were detected in 17.98% of the women, but these were not significantly associated with high-grade lesions.ConclusionThe greater protection of the nine-valent HPV vaccine is likely to have a positive impact because, in the absence of genotype 16 or 18 infection, these five genotypes on their own remained significantly associated with high-grade lesions.

ASC-H cytological result: clinical relevance and accuracy of colposcopy in predicting high-grade histological lesions—a 7-year experience of a single institution in Portugal

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) represents an interpretative challenge in clinical practice. We aimed to evaluate the histological outcome of ASC-H cytology and to evaluate the accuracy of colposcopy in predicting high-grade histological lesions. Retrospective study of ASC-H cervical cytology results, from January 2010 to December 2016, at a tertiary hospital. Demographic characteristics, colposcopic findings, diagnostic procedures, and histological outcomes were analyzed using SPSS, version 22.0. ASC-H prevalence was 0.25%. Patient mean age was 42.02 ± 12.8 years. The overall incidence of cervical dysplasia of any grade was 83.6% (n = 56) and the incidence of high-grade lesions was 50.8% (n= 34) (including 1 case of in situ adenocarcinoma and 2 cases of squamous cell carcinoma). Among patients with type 1 or 2 transformation zone (TZ), 84.9% (n = 45) had abnormal colposcopic findings, with 62.2% (n = 28) corresponding to grade 2 and 37.8% (n = 17) to grade 1. Colpo-histologic concordance was 85.4% (82.1% for grade 2 lesions and 100% for grade 1 lesions). The sensitivity, specificity, positive predicted value (PPV) and negative predictive value (NPV) was 100%, 75%, 82.1%, and 100%, respectively. The histological study of patients with type 3 TZ revealed 45.8% (n = 11) of high-grade lesions. ASC-H is strongly associated with high-grade histological lesions. Immediate evaluation of patients with this cytology abnormality is therefore mandatory. Colposcopy, when performed by expert clinicians, has great accuracy in detecting high-grade lesions. Histological evaluation of patients with type 3 TZ is extremely important because almost 50% of patients have this type of lesion.

Tumor Size is Associated With Malignant Potential in Renal Cell Carcinoma Cases

We evaluated our experience with renal cortical tumors to determine whether tumor size is associated with malignant histology and/or nuclear grade. We identified 2,675 patients treated surgically at our institution for renal cell carcinoma or a benign tumor between 1989 and 2007. Histological subtype and tumor size were obtained from our kidney cancer database and logistic regression analysis was performed. Of the 2,675 tumors 311 (12%) were benign and 2,364 (88%) were renal cell carcinoma. The OR for the association of malignancy with tumor size was 1.16 (95% CI 1.11-1.22, p <0.001), indicating that each 1 cm increase in tumor size was associated with a 16% increase in the odds of malignancy. The incidence of benign tumors decreased from 38% for tumors less than 1 cm to 7% for tumors 7 cm or greater. In patients with clear cell renal cell carcinoma each 1 cm increase in tumor size increased the odds of high grade disease (Fuhrman grade 3-4) compared with low grade disease (Fuhrman grade 1-2) by 25% (OR 1.25, 95% CI 1.21-1.30, p <0.001). In this subset the incidence of high grade lesions increased from 0% for tumors less than 1 cm to 59% for tumors greater than 7 cm. Our results confirm previous observations suggesting that the risks of malignancy and high grade tumors increase with tumor size. Patients with small renal masses are at low risk for harboring a high grade clear cell malignancy, which may be useful during initial consultation.

Ki-67 expression in anal intraepithelial neoplasia in AIDS.

AIDS is one of the most important risk factors for progression and recurrence of anogenital condyloma. In a previous work, we observed that patients with warts and high-grade AIN (HAIN) had recurrences more frequently than did patients with warts without AIN. The mechanisms of this increased incidence of high-grade lesions in AIDS are not known. We studied the expression of the proliferative marker Ki-67 by immunohistochemical methods, in specimens of anal condyloma from HIV+ patients to clarify whether its expression can be associated to the grade of AIN. A retrospective study of histological specimens. University referral unit. 34 patients were divided into two groups: (1) condylomas with low grade AIN (LAIN), with 25 patients; and (2) condylomas with HAIN, with 9 patients. In this latter group we examined two areas: 2A (HAIN area) and 2B (LAIN area). The immunohistochemical reaction for Ki-67 was done on histological sections. Slices were lightly stained with hematoxylin, to help us in Ki-67 positive cell counting. The percentage of Ki-67 marked nuclei was calculated. We applied one-way variance analysis for statistics. The mean number of Ki-67 positive cells in group 1 was 19.68 +/- 10.99; in group 2 (area A) it was 46.73 +/- 10.409; and in area B it was 36.43 +/- 14.731. There were statistical differences between groups 1 and 2A and between groups 1 and 2B. Ki-67 positive cells predominated in the lower layer in LAIN. Positive Ki-67 cells were found in all layers in group 2A, and in group 2B they predominated in the two lower or in all layers of the epithelium. Our results suggest that LAIN areas (using routine staining techniques) in HAIN can have a biological behavior more similar to HAIN.

Endometrial cancer. Management of high risk and recurrence including the tamoxifen controversy.

Risk factors for endometrial cancer include obesity, nulligravidity, late menopause, and anovulatory states. Although diabetes is highly associated with endometrial cancer, hypertension is not an independent variable when correction is made for other factors. Exogenous estrogen increases the risk by at least four times, and smoking is a significant factor. Screening of asymptomatic women may be useful among high risk patients. In addition, racial influence on virulence has recently been identified. Most recurrences of endometrial cancer are identified within 3 years of initial diagnosis. Predictors include ploidy, histologic grade, histologic type, receptor status, and stage. Treatment of recurrence is individualized based on tumor location and receptor status and may involve surgery, radiation therapy, hormonal therapy, or cytotoxic chemotherapy. Tamoxifen has been shown to improve survival among subsets of patients with breast cancer in all stages. A comprehensive literature review and meta-analyses, however, verified an increased risk of endometrial cancer among tamoxifen-treated patients compared with control subjects that may equal the cancer risk from exogenous estrogen exposure. Screening techniques include sonographic assessment of endometrial thickening and vascular patterns, hysteroscopy, and endometrial sampling. A subendometrial cystic proliferation can confuse radiographic evaluation of endometrium, leading to unindicated curettage. A disproportionate incidence of high grade lesions has been reported; however, tamoxifen should not be withheld from patients with breast cancer.

Impact of the Bethesda System.

Although the Bethesda System provides concise, specific descriptions for classifying cervical cytology, its usefulness has been questioned in the United States and abroad. The author attempted to evaluate the impact of the Bethesda System on cervical screening and subsequent management decisions. A MedLine search provided statistical information for comparison of screening procedures and results before and since introduction of the Bethesda System. The effect of the Bethesda System was evaluated by specimen adequacy, inclusion of human papillomavirus changes in the squamous intraepithelial lesion (SIL) category, and effect on the number of abnormal Pap smears. By 1992, 85% of cytology laboratories were using Bethesda system terminology. Diagnosis and treatment of patients with atypical squamous cells of undetermined significance (ASCUS) and low grade squamous intraepithelial lesions were reviewed. In women with ASCUS smears, follow-up studies showed that between 5% and 13% actually had high grade cervical lesions. For patients with a cytologic diagnosis of low grade SIL, one study found an 18.6% incidence of high grade lesions demonstrated by colposcopically directed cervical biopsy. An estimated 2% increase has occurred in the number of women with abnormal Pap smear results who require additional evaluation costing more than $1 billion. The Bethesda System has improved the quality of Pap smear diagnosis in the United States, but the number of women with abnormal Pap smear results has increased. Although this increase is partly due to the terminology of the Bethesda System, other factors play a role. Whether this has improved cancer prevention is unknown.