Analysis of the role of the human papillomavirus 16/18 E7 protein assay in screening for cervical intraepithelial neoplasia: a case control study.

BACKGROUND: Cervical cancer is the second-most common gynecological cancer, early screening plays a key role in the diagnosis and treatment of cervical intraepithelial neoplasia (CIN). Sustained E7 protein expression is the pathological basis for CIN and cervical cancer. METHODS: We collected the cervical cell samples of women who visited the gynecological clinic of Peking Union Medical College Hospital between September 2018 and September 2019 and submitted them to the high-risk human papillomavirus (Hr-HPV) test. We performed a magnetic particle-based chemiluminescence enzyme immunoassay to analyze the HPV16/18 E7 protein level in CIN of different severities and compared the results with those of cervical pathology (gold standard) and the HPV test. RESULTS: The positive rate of HPV16/18 E7 protein increased with the severity of CIN: 26.6% in normal tissue, 58.3% in CIN1, and 70.6% in CIN2 or higher (CIN2+). For CIN2+, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the E7 protein were 70.6, 67.9, 52.2, and 82.3%, respectively. These values of the HPV test were 86.8, 44.5, 43.7, and 87.1%, respectively. With the combination of the E7 protein assay and HPV test, the specificity for diagnosing CIN2+ was 78.1%, which was significantly higher than that of the HPV test alone. CONCLUSIONS: HPV16/18 E7 protein level is correlated with the severity of CIN and has a high concordance rate with the pathological result. For cervical cancer screening, the combination of HPV16/18 E7 protein assay and HPV test improves the CIN diagnostic specificity, detection rate, and detection accuracy.

A prospective study of treatments for cervical intraepithelial neoplasia and fecundability.

BACKGROUND: Treatments for cervical intraepithelial neoplasia remove precancerous cells from the cervix by excising or ablating the transformation zone. Most studies show no association between cervical intraepithelial neoplasia treatments and fertility outcomes. However, only 2 studies have examined time to pregnancy, both using retrospective study designs, with 1 study showing no association and the other showing a 2-fold increased risk of infertility (time to pregnancy >12 months) following excisional or ablative treatment. OBJECTIVE: We examined the association between cervical intraepithelial neoplasia treatments and fecundability. MATERIALS AND METHODS: We analyzed data from Pregnancy Study Online (PRESTO), a prospective cohort study of North American pregnancy planners enrolled during 2013-2019. At baseline, women reported whether they ever had an abnormal Papanicolaou test result, the number of abnormal Papanicolaou test results, and their age at first abnormal Papanicolaou test result. They also reported whether they underwent diagnostic (colposcopy) or treatment (excisional or ablative) procedures, and their age at each procedure. We restricted analyses to 8017 women with 6 or fewer cycles of attempt time at enrollment who reported receiving a Papanicolaou test in the previous 3 years. We estimated fecundability ratios and 95% confidence intervals using proportional probabilities models adjusted for sociodemographics, healthcare use, smoking, number of sexual partners, history of sexually transmitted infections, and human papillomavirus vaccination. RESULTS: A history of abnormal Papanicolaou test results showed little association with fecundability (fecundability ratio, 1.00; 95% confidence interval, 0.95-1.06). Likewise, receipt of colposcopy or treatment procedures, and time since treatment were not materially associated with fecundability. Results were similar when stratified by age and smoking status. CONCLUSION: We observed no appreciable association of self-reported history of abnormal Papanicolaou test results, colposcopy, treatments for cervical intraepithelial neoplasia, or recency of treatment with fecundability. These results agree with the majority of previous studies in indicating little effect of cervical intraepithelial neoplasia treatments on future fertility.

Sexual Activity, Psychosexual Distress, and Fear of Progression in Women With Human Papillomavirus-Related Premalignant Genital Lesions.

INTRODUCTION: Genital human papillomavirus (HPV) infections are very common in women 18 to 30 years old and substantially affect women's sexual health. AIM: To examine sexual activity, psychosexual distress, and fear of progression in women diagnosed with HPV-related precancerous genital lesions. METHODS: In this observational study, women diagnosed with premalignant lesions of the cervix, vagina, or vulva were recruited from a university hospital-based colposcopy clinic. MAIN OUTCOME MEASURES: Quantitative data from three validated patient-administered questionnaires (Sexual Activity Questionnaire, German version of the Cervical Dysplasia Distress Questionnaire, and Fear of Progression Questionnaire) were compared within the study population, according to the location of the genital lesion, and with relevant reference populations. Qualitative data from two written open-ended questions about women's thoughts regarding diagnosis and information were analyzed. RESULTS: Two-hundred nine women completed the questionnaires. Seventy-eight percent of women (n = 162) were referred for evaluation of suspect lesions of the cervix, 8% (n = 17) of the vagina, and 14% (n = 30) of the vulva. There were no significant differences in questionnaire results among the three patient groups, except for sexual consequences (Cervical Dysplasia Distress Questionnaire) and recent sexual activity (Sexual Activity Questionnaire). Women with vulvar lesions were most likely to worry about sexual consequences (ie, being unable to have children, being sexually less attractive, or infecting a sexual partner; P = .04). The Sexual Activity Questionnaire subscales sexual pleasure (P = .15) and sexual habits (P = 1.00) were similar to those in a healthy control population, whereas sexual discomfort (P = .51) was comparable to that in a reference population of women who survived cervical cancer. The subscale partner-specific concerns (Fear of Progression Questionnaire) was similar to that in a reference population of patients with cancer (P = .28). CONCLUSION: HPV-related precancerous genital lesions, especially of the vulva, are likely to cause concerns about sexual health. Effective information and communication are important to lessen negative sexual consequences and anxiety.

Recurrence of cervical intraepithelial lesions after thermo-coagulation in HIV-positive and HIV-negative Nigerian women.

BACKGROUND: The burden of cervical cancer remains huge globally, more so in sub-Saharan Africa. Effectiveness of screening, rates of recurrence following treatment and factors driving these in Africans have not been sufficiently studied. The purpose of this study therefore was to investigate factors associated with recurrence of cervical intraepithelial lesions following thermo-coagulation in HIV-positive and HIV-negative Nigerian women using Visual Inspection with Acetic Acid (VIA) or Lugol's Iodine (VILI) for diagnosis. METHODS: A retrospective cohort study was conducted, recruiting participants from the cervical cancer "see and treat" program of IHVN. Data from 6 sites collected over a 4-year period was used. Inclusion criteria were: age ≥18 years, baseline HIV status known, VIA or VILI positive and thermo-coagulation done. Logistic regression was performed to examine the proportion of women with recurrence and to examine factors associated with recurrence. RESULTS: Out of 177 women included in study, 67.8 % (120/177) were HIV-positive and 32.2 % (57/177) were HIV-negative. Recurrence occurred in 16.4 % (29/177) of participants; this was 18.3 % (22/120) in HIV-positive women compared to 12.3 % (7/57) in HIV-negative women but this difference was not statistically significant (p-value 0.31). Women aged ≥30 years were much less likely to develop recurrence, adjusted OR = 0.34 (95 % CI = 0.13, 0.92). Among HIV-positive women, CD4 count <200cells/mm(3) was associated with recurrence, adjusted OR = 5.47 (95 % CI = 1.24, 24.18). CONCLUSION: Recurrence of VIA or VILI positive lesions after thermo-coagulation occurs in a significant proportion of women. HIV-positive women with low CD4 counts are at increased risk of recurrent lesions and may be related to immunosuppression.

[Expression of miR-let-7e-3p in cervical intraepithelial neoplasm and cervix carcinoma and its clinical significance].

Objective: To investigate the expression of microRNA (miRNA, miR) let-7e-3p in different cervical lesions and its clinical significance. Methods: The expression of miR-let-7e-3p in the tissues of normal cervix (n=26), high-grade squamous intraepithelial lesion (HSIL) (n=37), and cervix carcinoma (n=101) were detected by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). The correlation of miR-let-7e-3p expression with the clinicopathological parameters of patients with cervical cancer was analyzed. miR-let-7e-3p mimic was transfected into cervical carcinoma Siha cells. The cell cycle and apoptosis were determined by flow cytometry; cell proliferation was determined by CCK-8 kit; and the migration and invasion of cells were determined by Transwell assay. Results: The relative expression levels of miR-let-7e-3p in normal cervix, HSIL, and cervical carcinoma were 1.45±0.24, 0.79±0.05 and 0.46±0.04, respectively (all P<0.05). After transfection with miR-let-7e-3p mimic, the S-phase fraction and apoptosis rate of Siha cells were increased significantly compared with control group[(29.76±6.6)% vs (13.38±1.3)%, P<0.05; (5.98±1.38)% vs (3.53±0.79)%, P<0.05, respectively]. OD of transfected Siha cells at 48, 72 and 96 h were 0.57±0.11,0.65±0.04 and 0.84±0.14, which were significantly lower than those of untransfected Siha cells (0.74±0.05, 0.93±0.10 and 1.47±0.14, all P<0.05). The migration and invasion abilities of transfected Siha cells were not significantly changed (all P>0.05). Conclusion: The expression of miR-let-7e-3p is down-regulated in cervical neoplasms, which is associated with cell cycle arrest and proliferation inhibition of cervical cancer cells.

Clinical progression of high-grade cervical intraepithelial neoplasia: estimating the time to preclinical cervical cancer from doubly censored national registry data.

Little is known about the time span of progression from high-grade cervical intraepithelial neoplasia (CIN2/3) to invasive cervical cancer. Estimation of this duration from longitudinal studies is not permitted, as CIN2/3 should be treated when detected. Cross-sectional data on the age-specific incidence of detected CIN2/3 and cervical cancer cases are readily available in national registries, but these data are difficult to interpret because neither the moment of lesion development nor the onset of invasive cancer is observed. We developed a statistical model for estimating the duration of time between CIN2/3 and preclinical cancer using Dutch national registries for the years 2000-2005. Human papillomavirus (HPV) genotype data were used to separate CIN2/3 and cancer incidences to obtain estimates for HPV-16-positive and HPV-16-negative lesions. The median time from CIN2/3 to cancer was estimated to be 23.5 years (95% confidence interval: 20.8, 26.6), and 1.6% of the lesions progressed to cancer within 10 years. The median duration for HPV-16-positive lesions was similar, but 2.4% of the HPV-16-positive lesions progressed to cancer within 10 years, as compared with 0.6% for HPV-16-negative lesions. Estimated durations of time to cancer are essential for reassessment of the optimal screening interval in light of vaccination and novel screening tests.

Prospective evaluation of the Amplicor HPV test for predicting progression of cervical intraepithelial neoplasia 2.

AIM: The aim of this study was to evaluate the clinical performance of the Amplicor HPV test, which detects 13 high-risk human papillomaviruses (HR-HPV), and to determine the association between consistent HR-HPV infection and progression of cervical intraepithelial neoplasia (CIN) 2 to CIN3. MATERIAL AND METHODS: This multi-institutional prospective study enrolled 122 women diagnosed with CIN2 by central pathological review. Subjects were tested at study entry and every 6 months over a 24-month period by cytology, Amplicor HPV test and colposcopy. Central pathological review was performed at the end of the study or if CIN progression was suspected. RESULTS: Ninety-three of the 122 participants completed all tests in the study and were included in the analysis. HR-HPV was detected in 87/93 (93.5%) participants at study entry. Twenty-four of the 87 HR-HPV-positive participants progressed to ≥CIN3, compared with none of the six participants who were HR-HPV-negative at study entry. The positive predictive value, negative predictive value, sensitivity and specificity of the Amplicor HPV test at study entry for predicting ≥CIN3 progression were 27.6%, 100%, 100% and 8.7%, respectively. Sixty-two participants were HR-HPV-positive from study entry through to study completion, 24 of whom progressed to ≥CIN3. None of 31 participants without continuous HR-HPV detection progressed to ≥CIN3. For continuous HR-HPV detection, the positive predictive value, negative predictive value, sensitivity and specificity of the Amplicor HPV test were 38.7%, 100%, 100% and 44.9%, respectively. CONCLUSIONS: All participants who progressed to ≥CIN3 were continuously HR-HPV-positive. The Amplicor HPV test thus demonstrated a good performance for predicting CIN3 progression.

Quality of life among Thai women diagnosed with cervical cancer and cervical intraepithelial neoplasia at King Chulalongkorn Memorial Hospital.

OBJECTIVE: To determine health related quality of life (QoL) of patients diagnosed with cervical intraepithelial neoplasia (CIN) and cervical cancer compared QoL among stages of cancer and to study the association between QoL and patients' characteristics. MATERIAL AND METHOD: The questionnaire elicited information and QoL using Functional Assessment of Cancer Therapy General (FACT-G) questionnaire. The study population was patients with a diagnosis of one of the four FIGO stages of cervical cancer RESULTS: One hundred seventy two patients completed the present study. The adjusted mean scores QoL was 78.76. There were no significant differences between FIGO stages on the global QoL and subscale. The authors found negative association between age and physical wellbeing scores (p = 0.049) and a positive association between age and emotional wellbeing scores (p = 0.004). Lower educational attainment was associated with higher emotional wellbeing scores (p = 0.004). CONCLUSION: For many patients, family, religion, or psycho-social support may be considered a necessity. The younger and better-educated groups may require more information and psycho-emotional support.

Optimal timing of the loop electrosurgical excision procedure according to different phases of the menstrual cycle.

OBJECTIVE: To determine whether treatment of cervical precancerous lesions in the follicular phase or luteal phase of the menstrual cycle affects perioperative and postoperative blood loss during the LEEP. METHODS: In this randomized trial, 73 patients were assigned to either the follicular phase group (n = 37) or the luteal phase group (n = 36). Ultimately, the conditions of 36 patients in the follicular phase group and 34 patients in the luteal phase group were analyzed. The primary outcome measure was median early postoperative blood loss. Secondary outcomes were median intraoperative bleeding, the rate of late postoperative bleeding, and persistent vaginal bleeding. RESULTS: Baseline demographic data were similar in the two groups. Median intraoperative blood loss was significantly lower in the follicular phase group than in the luteal phase group (32.7 [20.1-78.3] vs. 44.6 [30.4-104.2] mL, respectively; P < 0.001). Median early postoperative blood loss was also lower in the follicular phase group than in the luteal phase group (209.2 [67.7-468.6] vs. 289.0 [120.3-552.8] mL, respectively; P = 0.01). Moreover, the rate of late postoperative bleeding was higher in the luteal phase group than in the follicular phase group (20.6% vs. 2.8%, respectively; P = 0.02). CONCLUSION: Performing LEEP during the follicular phase of the menstrual cycle significantly reduces median intraoperative blood loss, early postoperative blood loss, and the rate of late postoperative blood loss.

Cytological, Colposcopic and Pathohistological Correlation of HSIL and ASC H Findings.

INTRODUCTION: Cervical cancer can be successfully prevented by timely detection of changes that precede it such as atypical (ASC-H) and high grade squamous lesions (HSIL). AIM: To investigate the correlation between Pap smear and colposcopy in the detection of premalignant and malignant cervical lesions based on a pathohistological finding. METHODS: In a retrospective study 118 patients with HSIL and ASC-H findings were examined. A Pap smear, colposcopic examination and cervical canal biopsy were performed. The study was conducted at the Gynecological Center "Dr Mahira Jahic" Tuzla and the Clinical Center Tuzla, Department of Gynecology and Obstetrics. RESULTS: 1049 abnormal Pap tests were analyzed, ASCUS in 51,8% (N-544), LSIL 32,1% (N-337), HSIL 7,7% (N-81) and ASC-H 3,5% (N-37), AGC 4,8% (N-51). The mean age of the subjects with the abnormal Pap test was 46.33 ± 3.2. The age of patients with ASCUS lesion was 38,6 , LSIL 41,0, ASC-H was 47,3 , HSIL (CIN II and CIN III) 45,8 , while patients with CIS were 51,2 years. Pathological histology HSIL confirmed a high grade lesion in 67,7% (CIN II, CIN III and CIS) (N-55), in 32% (N-26) a lower grade CIN I in 18,5% and chronic cervicitis in 13,5% (N-11). In ASC-H lesion pathohistological HSIL was found in 13,5% (N-5), CIN I 13,5% (N-5) and chronic cervicitis 48,6 % (N-18). Abnormal colposcopic imaging with HSIL lesion was found in 72,9% (N-69), in 8,6% (N-7) was unsatisfactory and in 18,5% (N-15) the colposcopic finding was normal. In ASC-H lesions, abnormal colposcopic imaging was found in 40,5% (N-15), unsatisfactory findings in 10,8% (N-4), and normal findings in 48,6% (N-18). CONCLUSION: Colposcopy has proven to be better method than cytology with an accuracy of 72,9% in high-grade lesion such as HSIL and ASC-H.

SARS-CoV-2 infection and impact on female genital tract: An untested hypothesis.

COVID pandemic consists one of the most challenging medical realities. Apart from affecting respiratory system, current evidence has demonstrated multiorgan manifestations that SARS-Cov-2 infection may actually have. However, one of the medical hypotheses not yet thoroughly tested is the impact on female reproductive system and more specifically cervix. No large observational studies have been performed to test presence of SARS-Cov-2 in cervical samples, while potential correlation and impact on HPV infection has not yet been examined. In this context, our research team has already planned to begin a prospective observational study regarding detection rates of SARS-CoV-2 genetic material in cervical cytology. The collected specimen will be analyzed for the presence of COVID-19 genetic material and in case of positive results, HPV typing will be performed as well in order to detect potential correlations between SARS-CoV-2 infection and HPV-infection. We would therefore like to launch our idea to control for SARS-CoV-2 infection in cervical specimen as well as examine potential correlation with HPV infection. Potential scientific proof of such hypothesis would change much regarding follow-up of HPV-positive patients while also triggering further research regarding aitiopathogenetic pathways of COVID. Communication of such a medical hypothesis could potentially motivate colleagues worldwide to expand their interest also on the research of SARS-CoV-2 cervical infection, in an effort to optimize our level of knowledge towards this new threatening and unknown reality of SARS-CoV-2.

Effects on Vaginal Microbiota Restoration and Cervical Epithelialization in Positive HPV Patients Undergoing Vaginal Treatment with Carboxy-Methyl-Beta-Glucan.

OBJECTIVE: Evaluate the effects of carboxy-methyl-beta-glucan on cervical epithelialization and on the vaginal microbiota in patients with HPV infection or low-grade cervical preneoplastic lesion (CIN 1). MATERIALS AND METHODS: Seven-hundred eighty-four women with positive HPV tests or diagnosed with CIN 1 were enrolled in a retrospective case-control study. All the recruited women performed, at baseline and after 6 months, Pap test, HPV test, evaluation of vaginal health according to the Amsel criteria, colposcopy, and punch biopsy. The study population was then divided into 2 groups in relation to the therapy performed during the follow-up period. Group A performed treatment with vaginal gel based on carboxy-methyl-beta-glucan (1 application/day for 20 days per month for 3 months). Group B was the control group. RESULTS: The patients of group A had a significant improvement in the ectopia pattern and a greater number of cases with metaplasia in the maturation phase with a significant increase in Lugol uptake. In the experimental group, a significant improvement in the pH indices, a negative Swift test and a resolution of the leucorrhoea were observed. A negative result of the 37.1% Pap test and the 39.9% HPV test (vs. 15.2% and 16.5%, respectively) were demonstrated in the treatment group with respect to the control group. A negativization of the colposcopic pictures was observed with a reduction in the amount of CIN 1 found higher in the treatment group. CONCLUSIONS: Vaginal therapy based on carboxy-methyl-beta-glucan has been able to improve overall vaginal health; this effect seemed to positively impact the risk of persistence and progression of CIN.

Biological behavior of CIN lesions is predictable by multiple parameter logistic regression models.

OBJECTIVES: Progression and regression of premalignant cervical lesions cannot be predicted using conventional cytomorphological or histomorphological parameters. However, markers such as human papillomavirus (HPV) or makers indicating proliferation, genetic instability and chromosomal aberration may be of predictive value assessing short-term biological behavior of cervical intraepithelial neoplasia. In this paper, we have studied the usage of logistic regression models with Ki-67 labeling index (LI), chromosome index for chromosome 1 (CI#1) and aneusomy for chromosome 1 in cervical smears to predict progressive and regressive behavior of premalignant cervical lesions. METHODS: Retrospectively, the intake smears of 42 women showing regression in follow-up and of 31 women showing progression in follow-up were assessed. RESULTS: A multiparameter logistic regression model containing the parameters Ki-67 LI, CI#1 and the fraction of cells with four copies of chromosome 1 per nucleus appeared to be the best predicting model, overall correct classification of 93.2% (area under the receiver operating characteristic curve 0.96 +/- 0.02). After cross-validation, the model correctly classified 66 of 73 samples (90.4%). Moreover, the model predicted biological behavior perfectly assessing the smear taken subsequently to the intake smear of 46 women. CONCLUSION: Although measuring parameters indicating proliferation and chromosome 1 aberration is laborious, this study demonstrates that short-term progressive and regressive behavior is highly predictable using a model combing these parameters. We also showed that in the triage management of high-risk human papillomavirus-positive women with minimally abnormal smears applying a model as such can be useful.

Apoptosis induction in Jurkat cells and sCD95 levels in women's sera are related with the risk of developing cervical cancer.

BACKGROUND: Currently, there is clear evidence that apoptosis plays an important role in the development and progression of tumors. One of the best characterized apoptosis triggering systems is the CD95/Fas/APO-1 pathway; previous reports have demonstrated high levels of soluble CD95 (sCD95) in serum of patients with some types of cancer. Cervical cancer is the second most common cancer among women worldwide. As a first step in an attempt to design a minimally invasive test to predict the risk of developing cervical cancer in patients with precancerous lesions, we used a simple assay based on the capacity of human serum to induce apoptosis in Jurkat cells. We evaluated the relationship between sCD95 levels and the ability to induce apoptosis in Jurkat cells in cervical cancer patients and controls. METHODS: Jurkat cells were exposed to serum from 63 women (20 healthy volunteers, 21 with cervical intraepithelial neoplasia grade I [CIN 1] and 22 with cervical-uterine carcinoma). The apoptotic rate was measured by flow cytometry using Annexin-V-Fluos and Propidium Iodide as markers. Serum levels of sCD95 and soluble CD95 ligand (sCD95L) were measured by ELISA kits. RESULTS: We found that serum from almost all healthy women induced apoptosis in Jurkat cells, while only fifty percent of the sera from women with CIN 1 induced cell death in Jurkat cells. Interestingly, only one serum sample from a patient with cervical-uterine cancer was able to induce apoptosis, the rest of the sera protected Jurkat cells from this killing. We were able to demonstrate that elimination of Jurkat cells was mediated by the CD95/Fas/Apo-1 apoptotic pathway. Furthermore, the serum levels of sCD95 measured by ELISA were significantly higher in women with cervical cancer. CONCLUSION: Our results demonstrate that there is a strong correlation between low levels of sCD95 in serum of normal women and higher apoptosis induction in Jurkat cells. We suggest that an analysis of the apoptotic rate induced by serum in Jurkat cells and the levels of sCD95 in serum could be helpful during the prognosis and treatment of women detected with precancerous lesions or cervical cancer.

Quantification of scattering changes using polarization-sensitive optical coherence tomography.

We demonstrate that changes in the degree of polarization (DOP) depend on changes in the scattering coefficient, and they can be quantified by using a polarization-sensitive optical coherence tomography (PS-OCT) system. We test our hypothesis using liquid and solid phantoms made from Intralipid suspensions and gelatin, respectively. We also quantify the DOP changes with depth caused by changes in the concentration of scatterers in the liquid and solid phantoms. It is clearly shown that the DOP change has a linear relationship with the scattering change. In our previous study, we showed that the axial slope of the DOP is different between normal and pathologic cervical tissues. Our results demonstrate that the quantification of the axial DOP slope can be used for the systematic diagnosis of certain tissue pathology.

New viral vaccines for dermatologic disease.

UNLABELLED: Two new viral vaccines have recently been approved by the Food and Drug Administration. Human papillomavirus (HPV) vaccine is intended to reduce infection with the most common HPV types that cause anogenital disease, including cervical cancer and genital warts. Herpes zoster (HZ) vaccine is intended to prevent shingles and its complications. The use of these two vaccines will immediately begin to impact dermatologic practice throughout the world and will reduce the healthcare burden associated with the diseases caused by the two viruses. The following review summarizes the relevant pathophysiology and epidemiology of genital warts, cervical neoplasia, and herpes zoster and describes the recent trials that have demonstrated efficacy and safety of the HPV and HZ vaccines. LEARNING OBJECTIVES: Following the completion of this learning activity, the participant will be able to describe the mechanisms of HPV and varicella zoster virus infection as well as pathogenesis, identify key aspects of the immune system involved in clearing the infection, and prescribe HPV and HZ vaccines for prevention of disease.

Natural history of cervical intraepithelial neoplasia during pregnancy.

OBJECTIVE: It is uncertain whether pregnancy influences the natural history of cervical intraepithelial neoplasia (CIN). Our aim was to evaluate the evolution of CIN in pregnant women. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynaecology, University of Insubria, Italy. POPULATION: Women with histological CIN during pregnancy. METHODS AND MAIN OUTCOME MEASURES: Between 2003 and 2007, women with an abnormal Pap-smear during pregnancy underwent colposcopy. Patients with histological CIN were followed during pregnancy with colposcopy every 8 weeks and post-partum evaluation was scheduled 3-6 months after delivery. Women with post-partum histological diagnosis of CIN 2-3 underwent conization. To understand the impact of pregnancy on the evolution of CIN, women with CIN 1 discovered during pregnancy were compared to a group of non-pregnant fertile patients with first diagnosis of CIN 1. RESULTS: A total of 78 women were included: 36 (46.2%) with CIN 2-3 and 42 (53.8%) with CIN 1. In women with CIN 2-3, no invasion was suspected during pregnancy and at post-partum evaluation, no invasive or microinvasive cancer, and 19 (52.7%) persistent CIN 2-3, and 17 (47.3%) regressions were diagnosed. In the group of CIN 1, we recorded six (14.3%) progressions to CIN 2-3, seven (16.6%) persistent CIN 1 and 29 (69%) regressions. The control group of non-pregnant women had a lower regression rate (37/76: 48.7%) in comparison to pregnant women (p=0.03). CONCLUSIONS: Expectant management for CIN 2-3 diagnosed during gestation is safe. When discovered during pregnancy, CIN 1 has a significantly higher tendency to spontaneous regression in comparison to non-pregnant condition.

Is cervical intra-epithelial neoplasia symptomatic?

Very little is known about cervical intra-epithelial neoplasia (CIN) and associated symptomatology. It is often quoted that that CIN is asymptomatic. We wanted to look at whether women with CIN were symptomatic or not. We are not aware of a similar study. We performed a case control study. Our cases were 22 women with abnormal cytology and histology results and our controls were 56 women who had been treated in the recent past and whose smears had returned to normal and those women whose smears had returned to normal spontaneously. Our study shows that there is no evidence that CIN is associated with post-coital bleeding, intermenstrual bleeding or discharge. Women with post-coital bleeding (PCB) are often fast tracked to the colposcopy clinic and women awaiting colposcopy suffer high levels of anxiety. There is no evidence for such practice.

The Association of Dietary Patterns with High-Risk Human Papillomavirus Infection and Cervical Cancer: A Cross-Sectional Study in Italy.

Specific foods and nutrients help prevent the progression of persistent high-risk human papillomavirus (hrHPV) infection to cervical cancer (CC). The aim of this study was to investigate dietary patterns which may be associated with hrHPV status and the risk of high-grade cervical intraepithelial neoplasia (CIN2+). Overall, 539 eligible women, including 127 with CIN2+, were enrolled in a cross-sectional study, and tested for hrHPV infection. Food intake was estimated using a food frequency questionnaire. Logistic regression models were applied. Using the Mediterranean Diet Score, we demonstrated that, among 252 women with a normal cervical epithelium, medium adherence to the Mediterranean diet decreased the odds of hrHPV infection when compared to low adherence (adjOR = 0.40, 95%CI = 0.22-0.73). Using the principal component analysis, we also identified two dietary patterns which explained 14.31% of the variance in food groups intake. Women in the third and fourth quartiles of the "Western pattern" had higher odds of hrHPV infection when compared with first quartile (adjOR = 1.77, 95% CI = 1.04-3.54 and adjOR = 1.97, 95%CI = 1.14-4.18, respectively). Adjusting for hrHPV status and age, women in the third quartile of the "prudent pattern" had lower odds of CIN2+ when compared with those in the first quartile (OR = 0.50, 95%CI = 0.26-0.98). Our study is the first to demonstrate the association of dietary patterns with hrHPV infection and CC and discourages unhealthy habits in favour of a Mediterranean-like diet.

The development of cervical cancer and its precursors: what is the role of human papillomavirus infection?

Human papillomavirus (HPV) is a significant health care burden in the United States. The majority of sexually active men and women will be infected with HPV at some point in their lives and are subject to developing human papillomavirus-associated disease. Current estimates suggest that 20 million Americans are currently infected, and more than 5 million new infections occur each year. The prevalence of human papillomavirus is highest in populations in their late teens and early twenties, with nearly half of all new human papillomavirus infections occurring within 3 years of first intercourse. HPV is the necessary cause of genital warts, cervical intraepithelial neoplasia, and invasive cervical cancer. As such, human papillomavirus is responsible for significant medical morbidity and health care costs. Screening with cervical cytology has significantly reduced mortality rates; however, approximately 3900 women will die in 2005 from cervical cancer in the United States. Human papillomavirus DNA testing has shown promise in identifying high-grade abnormalities as an adjunct to traditional cytology, and should be used according to guidelines established by the American Cancer Society and the American College of Obstetricians and Gynecologists. The epidemiology of HPV infection and a brief introduction to the natural history of HPV infection will be presented here.