Background & objectives: Human papillomavirus (HPV) is the necessary cause of cervical cancer and Chlamydia trachomatis (CT) is considered a potential cofactor in the development of cervical intraepithelial neoplasia (CIN). The objective of this pilot study was to determine the association of CT infection with HPV, other risk factors for cervical cancer, and CIN in symptomatic women.

Methods:

A total of 600 consecutively selected women aged 30-74 yr with persistent vaginal discharge, intermenstrual/postcoital bleeding or unhealthy cervix underwent conventional Pap smear, Hybrid Capture 2® (HC2) testing for HPV and CT DNA and colposcopy, with directed biopsy of all lesions.

Results:

HPV DNA was positive in 108 (18.0%) women, CT DNA in 29 (4.8%) women. HPV/CT co-infection was observed in only four (0.7%) women. Of the 127 (21.2%) women with Pap >ASCUS, 60 (47.2%) were HPV positive and four (3.1%) were CT positive. Of the 41 women with CIN1 lesions, 11 (26.8%) were HPV positive, while two were CT positive. Of the 46 women with CIN2+ on histopathology, 41 (89.1%) were HPV positive, two (4.3%) were CT positive and one was positive for both. The risk of CIN2+ disease was significantly increased (P<0.05) by the following factors: age <18 yr at first coitus, HPV infection and a positive Pap smear. Older age (>35 yr), higher parity, use of oral contraceptives or smoking did not show any significant association with HPV or abnormal histopathology. Parity >5 was the only risk factor positivity associated with CT infection (P<0.05). Interpretation & conclusions: Our findings showed that CT infection was not significantly associated with CIN, and most of its risk factors, including HPV infection, in symptomatic women. Longitudinal studies with carefully selected study sample would be able to answer these questions.

PURPOSE:

To create a prediction model of high-grade cervical intraepithelial neoplasia (CIN) based on clinical variables and the cervical nitric oxide metabolite (NOx) levels of study participants.

METHODS:

This comparative study included 694 women undergoing colposcopy due to abnormal pap smear results. On the basis of the cervical biopsy results, the women were divided into the ≤CIN 1 or CIN 2-3 group. The two groups were compared in terms of cervical NOx levels and clinical variables. Univariate, multivariate, and receiver-operating characteristic curve analysis were performed.

RESULTS:

Multivariate analysis showed that CIN 2-3 associated with more than two cervical biopsies [odds ratio (OR) = 5.16], high-grade squamous intraepithelial lesion cytology (OR = 16.19), condom non-use (OR = 4.28), cervical NOx levels ≤99.9 μmol/L (OR = 16.62), more than four lifetime male sexual partners (OR = 10.56), and age at first coitus of ≤15 years old (OR = 3.54). This combined model had a sensitivity of 86.49 %, a specificity of 90.74 %, a positive predictive value of 64.0 %, and a negative predictive value of 97.2 %.

CONCLUSIONS:

In the present sample, high-grade CIN associated with decreased cervical NOx levels. Thus, along with some clinical variables, cervical NOx levels may be an additional marker of cervical dysplasia.

The efforts of the authors are to evaluate the role of performing a Papanicolaou (Pap) smear at the time of colposcopy.This retrospective chart review included patients from 2004 to 2009 who underwent cold knife cone (CKC) biopsy or loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia types 2 and 3 (CIN 2 and 3) or patients with discrepancy between Pap and colposcopic results. All patients presented to the gynecology clinics in a tertiary care hospital. Results were compared which included: the abnormal Pap smear which led to referral for colposcopy, the Pap smear performed at the time of colposcopy, the colposcopic biopsy, and the excisional biopsy. Interpretation of results was calculated with Cohen's K Statistics.One hundred forty-seven patients qualified for the study. One hundred five patients had excisional biopsy proven high-grade squamous intraepithelial lesion (HSIL). Eighty-two of these high-grade excisional pathology results were preceded by high-grade Pap cytology at the time of colposcopy; however 23 Pap cytology results indicated either low-grade squamous intraepithelial lesion (LSIL) or negative (20 and 3 respectively), but were followed by an excisional procedure revealing high-grade pathology. Eighty-one colposcopic biopsies confirmed high-grade excisional biopsy pathology. However, 24 colposcopic biopsies were low-grade or negative (13 and 11 respectively), but followed by a high-grade excisional biopsy.The addition of a Pap smear at the time of colposcopy has the potential role of recognizing high-grade cervical dysplasia.

This study aimed to test the reliability of unaided naked-eye examination (UNEE) of the cervix as a sole cervical cancer screening test in a developing country setup compared with the standard cervical cytology.A total of 3,500 nonpregnant women aged between 25 and 55 years were included. An unlubricated bivalve speculum was inserted into the vagina under good light to visualize the cervix. A thorough UNEE of the cervix was done to detect any apparent lesions. Cervical smears were obtained using the long tip of an Ayre spatula. An additional endocervical sample was obtained by cytobrush. Women with abnormal Pap smears or visible cervical lesions by UNEE were scheduled for colposcopic examination. A biopsy specimen was obtained in every abnormal colposcopic examination.Of 3,500 cases, there were 9 (2.57%) preinvasive cervical lesions (cervical intraepithelial neoplasia 1-3) diagnosed with various diagnostic tools used in the study and confirmed by histopathologic examination. Of 3,500 cases, invasive cervical lesions were diagnosed in 6 (1.71%). The sensitivity of UNEE is much better than that of Pap smear (80% vs 60%) but less than that of colposcopy (86.7%). However, the specificity of UNEE (100%) is lower than that of Pap smear (91.16%) and better than that colposcopy (83.12%). The UNEE has a poor positive predictive value (3.75%) when compared with Pap smear (100%) and colposcopy (20%). The negative predictive values of the 3 tests were nearly comparable.Whenever access to Pap smear is limited, UNEE performed by general gynecologists and well-trained nurses is an acceptable alternative for detecting cervical premalignant or malignant lesions especially in low-resource settings.

OBJECTIVE:

Human papillomavirus (HPV) infections and abnormal Pap test results are common, and most do not progress to cervical cancer. Because it is difficult to predict which mild Pap abnormalities will develop into precancerous lesions, many women undergo painful and costly evaluations and even unnecessary treatment. The objective of this study was to develop a risk prediction model based on clinical and demographic information to identify women most likely to develop significant precancerous lesions (cervical intraepithelial neoplasia grades 2/3 [CIN 2/3] or adenocarcinoma in situ [AIS]) among women with mild Pap abnormalities (atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion).

MATERIALS AND METHODS:

The Abnormal Pap Smear Registry includes women who received treatment at the Brigham and Women's Hospital/Dana Farber Cancer Institute Pap Smear Evaluation Center beginning in 2006. It includes 1,072 women with mild cervical dysplasia (atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion) on their referral Pap test. We derived a clinical prediction model to predict the probability of developing CIN 2/3 or AIS using multivariate logistic regression with a split-sample approach.

RESULTS:

By the end of the follow-up, 93 of the 1,072 women developed CIN 2/3 or AIS (8.7%). There were several differences between women who developed CIN 2/3 or AIS and women who did not. However, once we put these into the regression model, the only variable that was significantly associated with CIN 2/3 or AIS was having a history of an abnormal Pap or biopsy result (odds ratio = 2.44; 95% CI =1.03-5.76). The resulting prediction model had poor discriminative ability and was poorly calibrated.

CONCLUSIONS:

Despite accounting for known risk factors, we were unable to predict individual patients' probability for progression on the basis of available data.

The aim of this paper is the evaluation of colposcopy and mRNA E6/E7 HPV detection--as the marker of persistent human papilloma virus (HPV) infection in the triage of abnormal Pap smears and in the assessment of cervical intraepithelial neoplasia progression risk. The clinical material consisted of 85 women, participating the national cervical cancer screening in the period of April 2010, and October 2010, reffered to the Outpatient Clinic of Gynecologic Oncology and Female Genital Tract Neoplasms Prophylaxy of the Jagiellonian University Medical College in Krakow, Poland. All subjects were offered gynecological evaluation, Pap smear, colposcopy, DNA HPV (Hybrid Capture2, Qiagen) and mRNA E6/E7 testing (NulciSens, Biomerieux). In case of positive tests colposcopically directed cervical biopsy with histopathologic evaluation were performed.

RESULTS:

The presence of mRNA E6/E7 HPV transcripts correlated with high grade squamous intraepithelial lesions, statistically significantly. There was statistically difference between colposcopic, histologic concordance comparing to mRNA E6/E7 HPV colposcopic histologic concordance (p < 0.001).

CONCLUSIONS:

The presence of mRNA E6/E7 HR HPV may be assumed as specific marker of high grade cervical lesions. The combination of mRNA E6/E7 HR HPV ewith colposcopic evaluation increases the colposcopy concordanece with final histologic findings.

BACKROUND: The incidence of abnormal cytological results in pregnant women is as much as 7%. Often there is need to advise pregnant women with an abnormal cervical cytology result and monitor them throughout pregnancy, without endangering the mother or child.

PATIENTS AND METHODS:

We retrospectively analyzed all pregnant women with an abnormal cervical cytology or condyloma in our dysplasia clinic between 01/2008 and 12/2011. Classification of the cervical cytological results was performed according to the Munich II nomenclature and a biopsy was obtained from most patients. Groups were defined in order to assess regression, persistence and progression. Particular attention was paid to the mode of delivery and the postpartum consultation.

RESULTS:

A total of 65 pregnant women were treated in the dysplasia clinic. The reason for referral was Pap IIID in 46.2%, Pap IVa in 40% and Pap III or Pap II with condyloma in 6.2% patients. Only one patient presented with a Pap IVb finding. The pregnancy was continued in all but one cases. Postpartum, a total of 40% of cases, were in remission. A partial remission occurred in 4.6%. Persistence of the abnormalities was observed in 26.2%. Progression was documented in 3% and 71.1% were able to have a vaginal delivery. A caesarean section was performed in 22.2%. A total of 4.4% suffered a miscarriage, which was not caused by the colposcopy. Discussion: The distinctive feature of the present study is the high number of follow-up examinations, which showed that even women with highly dysplastic changes in pregnancy, who are regularly monitored can be advised to continue pregnancy. Vaginal delivery is possible in most cases.

The aim of the study was to assess the diagnostic value of pap smears and detection of the p16 and Ki67 proteins in women with cervical intraepithelial neoplasia (CIN).630 women, aged between 25 and 65, with abnormal pap smears were included into the study All patients had a control pap smear and in each case punch biopsy with endocervical curettage were performed under the control of a colposcope. The presence of p16 and Ki67 proteins was detected using the CINtecPlus test. The results of the research were statistically assessed.Abnormal pap smears were found in 82.5% (520/630) of the studied women. In 40% (252/630) of the cases the LSIL changes were found. The recognition of ASC-US concerned 35.2% (222/630) of the patients, and pap smears with the HSIL result were found in 7.3% (46/630) of the women. In 17.5% (110/630) of the patients the result of the cytological examination was normal. Abnormal results of the pap smears were found significantly statistically more frequently (p<0,0001) in women with cervical intraepithelial neoplasia (CIN). The results of the CINtecPlus test were positive in 68,4% of women with CIN and in 33,3% of patients with normal cervix. In the group of women with precancerous lesions (HGSIL/CIN2+) the diagnostic accuracy of the pap smear was 41% for the cytological results ASC-US, 56% LSIL and 73% for detection of HSIL. Immunocytochemical detection of p16 and Ki67 proteins gained the highest accuracy (78%) in recognition of cervical precancerous lesions.1. ASC-US and LSIL cytological recognition has low accuracy in the diagnosis of CIN2+ cervical changes. 2. Cytological recognition of HSIL has the highest accuracy in the diagnosis of CIN2+ changes. 3. Immunocytochemical detection of p16 and Ki67 proteins is more accurate in recognizing precancerous states and cervical cancer than cytological examination. 4. Immunocytochemical detection of the p16 and Ki67 proteins can be used to triage patients with atypical squamous cells of undetermined significance and low grade squamous intraepithelial lesions.

K. Sigurdsson Is a liquid-based cytology more sensitive than a conventional Pap smear?

Background:

  The comparative sensitivity of liquid-based cytology (LBC) test and conventional Papanicolaou (Pap) smears is controversial. Material and methods:  This study analyses the distribution of cytology, histology, colposcopy and large loop excision of the transformation zone among women screened in Iceland with LBC at the Cancer Detection Clinic in Reykjavik and with a conventional Pap smear outside the Detection Clinic in 2007-2011. The study material included 42 654 LBC tests from 20 439 women and 103 909 Pap smears from 61 574 women. The period 2000-2004 is used to correct for potential bias as a result of unequal distribution of the studied parameters between the study sites before the introduction of LBC.

Results:

  The observed results indicated that women screened with an LBC sample had significantly decreased detection rates of inadequate smears, increased detection of low-grade squamous intraepithelial lesion (LSIL)/atypical cytology and referrals to colposcopy, and an increased detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) irrespective of age. LBC increased significantly the detection rates of high-grade squamous intraepithelial lesion or worse (HSIL+) cytology and CIN3+ histology only in women under 40 years of age. Taking into consideration the unequal prevalence of the studied parameters between the study sites in 2000-2004 indicated, however, that LBC only affected the rate of inadequate and low-grade cytology tests under the age of 40 years. Positive predictive values for CIN2+ were not significantly different between the tests.

Conclusions:

  The study results support the view that LBC is no more sensitive than Pap smears for the detection of HSIL+ and CIN2+ irrespective of age. LBC decreased the rate of inadequate smears, but increased the rate of low-grade cytology under the age of 40 years and decreased the total rate of abnormal smears over the age of 40 years.

It is well-known that persistent cervical infections with high-risk human papillomavirus (HPV) are related to the development of high-grade cervical intraepithelial neoplasia and invasive cervical cancer and that infection with HPV 16 and HPV 18 accounts for approximately 70% of all cases of invasive cervical cancer.We performed 3 HPV molecular tests-the Cobas 4800 HPV test, the Seeplex HPV4A ACE, and the hybrid capture 2 (HC2) test-in 146 cervical swab samples to compare between these three tests.There was a concordance rate of 82.8% between the results of the Cobas 4800 HPV and the HC2 test and a concordance rate of 84.9% between the results of the Seeplex HPV4A ACE and the HC2 test. Between the Cobas 4800 HPV test and the Seeplex HPV4A ACE, there was a concordance rate of 89.6% in the detection of high-risk HPV between the results and a concordance rate of 98.7% in the detection of HPV 16 or 18. When an abnormal Pap test was defined as ≥ low grade squamous intraepithelial lesion (LSIL), the sensitivity of the Cobas 4800 HPV test, the Seeplex HPV4A ACE and the HC2 test were 71.1%, 80.0%, and 88.9%, respectively, while their specificities were 76.4%, 74.5%, and 67.9%, respectively.The results of this study suggest that the Cobas 4800 HPV test and the Seeplex HPV4A ACE may be as effective as the HC2 test in detecting HR HPV and that the concordance between the results of the Cobas 4800 HPV test and the Seeplex HDV4A ACE may be higher in the detection of HPV 16 and HPV18 than concerning high-risk HPV.