Bacterial vaginosis as a risk factor for high-grade cervical lesions and cancer in HIV-seropositive women

Objective

To assess the effect of bacterial vaginosis (BV) on the risk of high-grade squamous intraepithelial lesions (HSIL) among HIV-seropositive women.

Methods

A hospital-based prospective cohort study of HIV-seropositive women was conducted in Johannesburg, South Africa from January 2005 to September 2009. Multivariate log-binomial and Poisson regressions were used to estimate prevalence and rate ratios, respectively.

Results

Among 1954 HIV-seropositive women, the baseline prevalence of HSIL was 17%. BV prevalence was high (54%) and showed no association with prevalence of HSIL (adjusted prevalence ratio, 1.12; 95% confidence intervals (CI), 0.92-1.35) nor with cervical lesion progression at follow-up visit (n = 503) (adjusted rate ratio: 1.00; 95% CI, 0.65-1.53).

Conclusion

Among HIV-seropositive women, BV was not associated with an increased risk of HSIL or cervical lesion progression.     

MicroRNA miR-886-5p inhibits apoptosis by down-regulating Bax expression in human cervical carcinoma cells

Objective

MicroRNA (miRNA) plays an essential role in the progression of a variety of cancers, but its role in cervical cancer progression is not well defined. We aimed to test whether special miRNAs and their target mRNAs contribute to cervical cancer progression.

Methods

The expression profiles of 1145 microRNAs in cervical squamous cell carcinomas (CSCC) and adjacent non-tumor tissues were investigated using an Illumina microRNA microarray platform. Differentially expressed miRNAs were validated by RT-PCR. Downstream target validation was performed for miR-886-5p.

Results

We found that the expression levels of seven miRNAs differed significantly between CSCC tissues and adjacent non-tumor tissues. Forced expression of one miRNA, miR-886-5p, over-expressed in CSCC tissues lowered expression of the pro-apoptotic protein Bax, reduced apoptosis and promoted cell proliferation in H8, an HPV16-immortalized human cervical squamous epithelial cell line. Knockdown of miR-886-5p increased Bax protein and apoptotic cell death in cells of the cervical squamous carcinoma cell line, SiHa.

Conclusion

MicroRNA miR-886-5p inhibits apoptosis of cervical cancer cells by down-regulating the production of Bax.     

Prevalence of HPV infection by cervical cytologic status in Brazil

Objectives

To assess the prevalence of human papillomavirus (HPV) infection according to cervical cytologic status in northeastern Brazil; identify other risk factors for low- and high-grade squamous intraepithelial lesions (LSILs and HSILs); and identify the most prevalent HPV genotypes associated with the lesions.

Method

Two cervical smears were collected from 250 women referred for cancer screening, one for cytologic examination and the other to test for the presence of HPV by PCR with genotyping by dot blot hybridization.

Result

There were 110 healthy cervices, 82 LSILs, and 58 HSILs. The overall HPV prevalence was 48%, with higher rates for HSILs, and HPV-16 was the most prevalent type. Age, multiple sexual partners, type of HPV present, smoking, and early onset of sexual activity were risk factors for cervical lesions.

Conclusion

Age, multiple sexual partners, and infection with HPV-16 increased the risk of having LSILs or HSILs. Early onset of sexual activity and smoking only increased the risk of having HSILs.     

Correlation between LRIG1 and LRIG2 expressions and expression of 11 tumor markers, with special reference to tumor suppressors, in CIN and normal cervical epithelium

Objective

Novel biological markers LRIG1 and LRIG2 have been associated with favorable as well as poor prognosis, respectively, in different cancer types, including cervical cancer. The aim of this study was to investigate possible interactions between these proteins and other tumor markers, and as diagnostic adjuncts in CIN.

Methods

Cervical biopsies from 171 women, with normal epithelium, and low-grade and high-grade CIN were stained for LRIG1 and LRIG2, and 11 additional tumor markers. The tumor markers were chosen to be relevant in cervical neoplasms. Staining was evaluated semiquantitatively.

Results

Expression of LRIG1 and LRIG2 was found to correlate with increasing CIN grade, as well as with expression of tumor suppressor FHIT, independent of histological grade. In addition, tumor promoter LRIG2 expression correlated negatively with expression of tumor suppressor retinoblastoma protein and positively with IL-10. The latter correlation did not however remain after adjustment for CIN grade. p53 and p16 expressions correlated positively with LRIG1 expression in univariate analyses, but significance did not hold after adjustment for CIN grade.

Conclusion

LRIG1 and LRIG2 expressions were seen in precancerous cervical epithelium and found to increase with increasing grade. There was an association between expression of these glycoproteins and FHIT tumor suppressor protein, independently of histological grade.     

p16/Ki-67 dual staining in cervico-vaginal cytology: correlation with histology, Human Papillomavirus detection and genotyping in women undergoing colposcopy

Objectives

To evaluate the CINtec® PLUS assay (mtm laboratories), a new immunocytochemical method for the simultaneous detection of p16^INK4a and Ki-67, in liquid-based cervico-vaginal cytology, investigating the association of the dual staining with HPV infection and genotyping as well as cytological and histological abnormalities.

Methods

140 women with a cervico-vaginal sample obtained immediately before the colposcopy were enrolled. This cytological sample was used for HPV testing with the Linear Array HPV Genotyping Test, the dual staining with the CINtec® PLUS kit and the morphology assessment.

Results

Cytology results were 38 NILM, 16 ASC-US, 32L-SIL, 54H-SIL or worse. 113 patients also had a colposcopy-guided biopsy, classified as 14 negative, 35 CIN1, 24 CIN2, 37 CIN3, 3 invasive SCC. A strong association between p16/Ki-67 and HR-HPV infection was found (COR = 6.86, 95% CI: 1.84-31.14). Importantly, the association between p16/Ki-67 positivity and HPV16 and/or 18 infection was 2-fold stronger compared to that with the infection by other HR-HPV types (COR = 9.92, 95% CI: 2.39-47.77 vs COR = 4.20, 95% CI: 0.99-20.87). In addition, p16/Ki-67 positivity rate significantly increased with the severity of the cytological and histological abnormalities (p < 0.05 in both cases). p16/Ki-67 positivity resulted strongly associated with a CIN2 + diagnosis (COR = 10.86 95% CI: 4.16-29.12).

Conclusions

This preliminary study evidenced that p16/Ki-67 immunostaining might have a relevant clinical role, since the dual staining was significantly associated with HR-HPV infection, particularly with HPV 16 and 18, and the increasing grade of the cervical lesions, the positivity for this biomarker being strongly related to the presence of a CIN2 + lesion.     

La morbilidad de la histerectomía radical como variable de resultado combinada

Objective

To assess serious morbidity after abdominal or laparoscopic radical hysterectomy, viewed as a composite endpoint.

Subjects and methods

We reviewed 41 abdominal radical hysterectomies performed at the San Dureta Hospital, Palma de Mallorca, between 2001 and 2007. Other publications were used as comparative pattern and to establish the components of the composite endpoint. The life table method was used to calculate the proportion of surviving patients. Confidence intervals (CI) of the proportion of patients with morbidity were calculated.

Results

Six-year survival was 85%. One serious complication was observed in every 21 patients (95% CI, 1.35-16.14%).

Conclusions

Serious morbidity associated with abdominal radical hysterectomy and laparoscopic radical hysterectomy can be similar.     

Clinical, colposcopic and pathological characteristics of cervical and vaginal high-grade lesions negative for HPV by Hybrid Capture 2

Objective

Less than 5% of women with cervical or vaginal biopsy proven high-grade squamous intraepithelial lesions (HG-SIL) show a negative Hybrid Capture 2 (HC2) result. We analyzed 1) human papillomavirus (HPV) genotypes by PCR in order to determine whether these cases represent infections by common or unusual types, and 2) the clinical, colposcopic and pathological differential characteristics of these patients.

Methods

646 women with a histological diagnosis of HG-SIL and a HC2 test collected within 6 months prior to the diagnosis were identified. Patients with a negative HC2 result were selected. HPV was typed in the biopsy specimen in all by PCR using SPF10 and GP5+/6+ primers, and p16^INK4a immunostaining was performed. The clinical and colposcopy findings of these women were compared with a control group of HG-SIL with positive HC2 result.

Results

20 women (3.1%) with HG-SIL had a negative HC2. All biopsies were positive for p16^INK4. PCR analysis detected HPV types included in HC2 test in 55% of the cases, with an identical percentage of common viruses between women with relative light unit values above or below 0.40 (p = .361). False negative HC2 tests increased with age (p = .002) and were more frequent in patients with non satisfactory colposcopy or small sized lesions (p < .001).

Conclusion

A negative HC2 test is an infrequent event in women with HG-SIL. Common HPV types are identified in over half of the cases. Older women and patients with small lesions or non satisfactory colposcopy have a higher rate of HC2 negative results.     

Análisis comparativo de dos protocolos de misoprostol en abortos de segundo trimestre de la gestación

Objective

To compare the mean induction-expulsion times in two regimens of vaginal misoprostol for second-trimester pregnancy termination.

Material and methods

We performed a retrospective study of 281 pregnancies between January 2000 and December 2005 (regimen A: 800 μg /24 h) and between June 2007 and December 2008 (regimen B: 400 μg /4 h). Induction-expulsion time was taken as the main outcome.

Results

The mean expulsion time was similar in both regimens (19.7 h for A and 17.7 h for B). No significant differences were found in the expulsion rate at 12, 24 and 48 h. The most commonly observed adverse effect was fever, which was more frequent in regimen B. No major adverse effects such as uterine rupture or severe hemorrhage were observed.

Conclusions

No significant differences were found between regimens A and B in the mean fetal expulsion time, although fever was more common in regimen B.     

Abnormal distribution of hDlg and PTEN in premalignant lesions and invasive cervical cancer

Objective

The aim of the present study was to evaluate differences in expression levels and localization status of PTEN, p53 and hDlg suppressor proteins in premalignant lesions and cervical cancer, and to analyze the possible correlation between them.

Methods

Expression levels (positivity/intensity) and localization (nuclear, membrane or cytoplasmic) of PTEN, hDlg and p53 were analyzed by immunohistochemistry in 43 cases with different stages of cervical intraepithelial neoplasia (CIN) and 105 invasive cervical carcinomas (ICC) (91 squamous carcinoma, 14 adenocarcinoma). Differences between proportions were evaluated.

Results

We found a decreased expression of PTEN in ICC that correlated with a loss of hDlg from the cell membrane. In contrast, no changes were found in p53 protein levels or localization in CIN and ICC.

Conclusions

These results suggest that the abnormal expression and localization of PTEN during cervical carcinogenesis may be a consequence of modifications in the expression patterns of hDlg.     

Centile charts of cervical length between 18 and 32 weeks of gestation

Objective

To establish a centile chart of cervical length between 18 and 32 weeks of gestation in a low-risk population of women.

Methods

A prospective longitudinal cohort study of women with a low risk, singleton pregnancy using public healthcare facilities in Cape Town, South Africa. Transvaginal measurement of cervical length was performed between 16 and 32 weeks of gestation and used to construct centile charts. The distribution of cervical length was determined for gestational ages and was used to establish estimates of longitudinal percentiles. Centile charts were constructed for nulliparous and multiparous women together and separately.

Results

Centile estimation was based on data from 344 women. Percentiles showed progressive cervical shortening with increasing gestational age. Averaged over the entire follow-up period, mean cervical length was 1.5 mm shorter in nulliparous women compared with multiparous women (95% CI, 0.4-2.6).

Conclusions

Establishment of longitudinal reference values of cervical length in a low-risk population will contribute toward a better understanding of cervical length in women at risk for preterm labor.     

High-grade histologic lesions in women with low-grade squamous intraepithelial lesion cytology from a region of Thailand with a high incidence of cervical cancer

Objective

To evaluate the prevalence of and predictors for underlying significant lesions in women with low-grade squamous intraepithelial lesion (LSIL) smears.

Methods

Records were retrospectively reviewed for 208 women with LSIL who underwent colposcopy and histological evaluation from October 2004 through April 2009.

Results

Mean age of the patients was 38.5 years. Forty-four (21.2%) women were nulliparous; 20 (9.6%) women were postmenopausal; 29 (13.9%) women tested positive for HIV. Thirty-three (15.9%) women were current users of combined oral contraceptive pills. The pathological results of initial colposcopic evaluations were: 63 (30.3%) with cervical intraepithelial neoplasia (CIN) 2-3; 62 (29.8%) with CIN 1; 4 (1.9%) with cervical cancer; and 79 (38.0%) with no epithelial lesion. Current use of combined oral contraceptive pills, a positive HIV test, and multiparity were significant independent predictors for high-grade disease.

Conclusion

Approximately one-third of women with LSIL in our population have underlying significant lesions. Current use of combined oral contraceptive pills, a positive HIV test, and multiparity are significant predictors for high-grade lesions.     

Evaluation of a single-step diagnosis and treatment of premalignant cervical lesion by LEEP

Objective

To explore whether a single-step diagnosis and treatment of premalignant cervical lesions by the loop electrosurgical excision procedure (LEEP) is appropriate in women at high risk in low-resource countries.

Method

Sixty women suspected of having a high-grade lesion on both visual inspection with acetic acid (VIA) and colposcopic examination were randomly allotted to one of 2 groups. In group 1, LEEP was performed immediately and a tissue specimen was sent for histopathologic evaluation; in group 2, a punch biopsy was performed, followed by a histopathologic evaluation; then, LEEP was performed if needed.

Results

Among the patients who underwent LEEP, 4 (16%) in group 1 and 3 (15.8%) in group 2 were overtreated. No patients dropped out of the study in group 1 but 5 (20.8%) did in group 2.

Conclusion

The single-step diagnosis and LEEP treatment of premalignant cervical lesions is appropriate in low-resource countries.     

HPV genotyping from invasive cervical cancer in Chile

Objective

To determine the prevalence rates of the different HPV types in cervical cancer lesions in Chile to facilitate the development of prophylactic human papillomavirus (HPV) vaccines effective for that country.

Method

Biopsy samples of 312 cervical cancer lesions were assessed for HPV type by reverse-line blotting assay.

Results

HPV DNA was found in 94.2% of the lesions, 67.2% harboring 1 viral type and the remainder harboring more than 1 type. HPV-16 was the most frequent type in single infections (50.5%), followed by HPV-18 (7.8%), HPV-31 (2.4%), and HPV-45 (2.0%). HPV-16 was also present in 98.7% of dual and multiple infections, its most frequent association being with HPV-18.

Conclusions

HPV types 16, 18, 31, and 45, alone or combined with other types, were observed in the biopsy samples of up to 80.5% of cervical cancer lesions.     

Human papillomavirus as a favorable prognostic biomarker in squamous cell carcinomas of the vagina

Objective

Recent evidence has confirmed two independent pathways in the development of vaginal squamous cell carcinoma (VaSCC): one related to and the other independent of human papillomavirus (HPV). The aim of our study was to evaluate whether HPV status has prognostic significance in this neoplasm.

Methods

All confirmed primary VaSCCs diagnosed and treated from 1995 to 2009 in two institutions were retrospectively evaluated (n = 57). HPV infection was detected by PCR using SPF-10 primers and typed with the INNO-LIPA HPV assay and p16^INK4a expression by immunohistochemistry. Disease-free and overall survival (DFS and OS) were analyzed by Kaplan-Meier analysis with the log-rank test and a multivariate Cox proportional hazard's model.

Results

HR-HPV DNA was detected in 70.2% patients. HPV16 was the most prevalent genotype (67.5% of cases). p16^INK4a was positive in 97.5% HPV-positive and 17.6% HPV-negative tumors (p < .001). FIGO stage was associated with DFS (p = .042) and OS (p = .008). HPV-positive tumors showed better DFS (p = .042) and OS (p = .035) than HPV-negative tumors. Multivariate analysis confirmed better DFS and OS of HPV-positive patients independent of age and stage. This reduced risk of progression and mortality in HPV-positive patients was limited to women with FIGO stages I and II tumors (HR = 0.26; 95% CI 0.10-0.69; p = 0.006).

Conclusions

HPV-positive early stage (FIGO I and II) VaSCCs have a better prognosis than early HPV-negative tumors. HPV detection and/or p16^INK4a immunostaining can be easily implemented in routine pathology and should be considered as valuable prognostic biomarkers in the study of patients with VaSCC.     

Invasión del espacio linfovascular en lesión intraepitelial escamosa de alto grado de cérvix. ¿Realidad o artefacto?

Background

The loop electro excision procedure is a simple and widely used diagnostic and therapeutic technique in cervical lesions. This procedure is usually performed in the ambulatory setting under local anaesthesia.

Subjects and methods

We describe a case of lymphovascular space invasion detected in the cone biopsy of a high-grade squamous intraepithelial lesion of the cervix.

Conclusions

Although the prognostic significance of LVSI is controversial, its identification precludes conservative treatments.     

Modificaciones del flujo sanguíneo de las arterias uterina, umbilical y cerebral media fetal en preeclámpticas tratadas con parches de nitroglicerina

Objective

To identify modifications in blood flow in uterine, umbilical and fetal middle cerebral arteries in preeclamptic patients treated with nitroglycerin patches.

Method

The sample consisted of 31 preeclamptic nulliparous patients with pregnancies of more than 25 weeks who attended the obstetric emergency service at the Dr. Urquinaona Central Hospital. The pulsatility index, resistance index and systolic/diastolic blood flow ratio of uterine, umbilical and fetal middle cerebral arteries were measured before treatment and after 24 and 48 h of treatment administration. Treatment consisted of 5 mg transdermal nitroglycerin patches, applied in the anterior thoracic and lumbar region of patients for 12 h (total time of 48 h).

Results

The pulsatility index, resistance index and systolic/diastolic blood flow ratio significantly decreased after the use of nitroglycerin patches (p<0.05). There were no significant modifications in the umbilical and fetal middle cerebral arteries at 24 and 48 h when compared with initial values (p=ns). There were no adverse effects.

Conclusion

Nitroglycerin patches decreased resistance to blood flow in the uterine arteries of preeclamptic patients without producing significant modifications in the umbilical and fetal middle cerebral arteries.     

Cáncer de cérvix metastásico y gestación: una situación poco frecuente que invita a la reflexión

Background

Coexistence of pregnancy and metastasic cervical cancer in an exceptional situation that will mark, in the presented case, the evolution of the pregnancy.

Case

A 34-year-old woman, gravida 2 para 1, at 13 weeks’ gestation was taken to our emergency service with menorragia, and was admitted under the suspicion of invasive cervical cancer. Patient?s evolution was complicated by the detection of supraclavicular metastasis and massive pulmonary tromboembolism. The patient decides voluntary interruption of pregnancy in the 17^th week.

Conclusions

This is a very unusual case, not as much the presence of an early stage cervical cancer in a pregnant woman. It reminds us of the need to carry out the mandatory gynecological exploration and smear in the first visit of prenatal care, often omitted in our dayly practice.     

Conizacion con asas diatermias en lesiones premalignas de cuello uterino

Objective

To compare the effectiveness of uterine conization in high-grade cervical squamous intraepithelial lesions (HSIL) by means of surgical electrical excision with Trucone loop or Leep loop.

Subjects and methods

We performed a comparative study that included 150 patients, aged between 20 and 45 years, with a diagnosis of HSIL. All patients underwent uterine conization with diathermy loop. The patients were separated into two groups according to the type of loop used.

Results

Both loops were effective in the management of HSIL but significant differences were found in favor of the Trucone loop in surgical time (X: 3.7 ± 0.52, p < 0.01), lesser margin involvement (100% free margins, p < 0.05) and a lower frequency of residual lesions (94.7%, p > 0.01).

Conclusions

Both diathermy loops were effective in the treatment of HSIL but the frequency of complications and residual lesions was lower with the Trucone loop.