Cervical Cytology and HPV Test in Follow-up after Conisation or LLETZ

The patients treated with conservative surgical therapy for cervical intraepithelial neoplasia (CIN) have an increased risk to develop invasive cervical carcinoma compared to the general population. Cervical cytology and HPV test are included in the protocols for the detection of treatment failure. The purpose of the study was to analyse cytology-histology correlation after conisation or Large Loop Excision of the Transformation Zone (LLETZ), resection margin status, compliance to the follow-up protocol and evaluation of cervical cytology and HPV testing in two year period after surgical treatment. We retrospectively reviewed 251 cases of conisation or LLETZ performed between January and December, 2006. Conventional cervical smears were analysed and abnormal cytology was defined as atypical squamous cells of undetermined significance or worse (ASCUS+). The digene Hybrid capture 2 test was used for detection of high-risk HPV types. Histology analysis demonstrated CIN1+ lesion in 234 cases (93.2%) with cytology-histology correlation in 97.9% of cases. A preoperative HPV test was made in 142 histologically confirmed CIN1+ lesions and 137 (96.5%) tested positive. The resection margins were involved in 48 (20.8%) cases. In 24 (10.3%) cases the margins were difficult to determine. Abnormal cytology was found in 33 (15.2%) cases of the 217 (86.5%) patients that attended the post-treatment visits. The post-treatment HPV test was performed on 159 women and it was positive in 25 (15.7%) cases. The complete follow-up control cytology, with at least three Pap smears in the subsequent two years or with second treatment, was registered in only 146 (58.2%) patients. 14/217 (6.5%) patients underwent second treatment with histologically confirmed treatment failure. In all patients with control smear, repeated cytology found HSIL. On six women, the control HPV test was performed. In five cases, it was positive and in one case with histological diagnoses of VAIN2, it was negative. Our study confirms the important role of cervical cytology in the diagnosis of cervical intraepithelial lesions and monitoring after treatment. In the future we will have to improve compliance to the follow-up protocols and use of the HPV test in the selection of women at risk of treatment failure

Zagreb 2016 classification of cervical cytology findings – modification of Zagreb 2002 and NCI Bethesda System 2014 classifications

The objective of the Zagreb 2016 classification as the third modification of the unique classification of cervical cytology findings based on the previous Zagreb 2002 and the latest Bethesda 2014 classifications is standardization of cervical cytology findings for the whole Croatia, according to the latest concepts on the biologic behavior of cervical cancer and its precursors. Besides cytomorphological lesions, Zagreb 2016 includes recommendations for diagnostic therapeutic procedures in line with the international recommendations and the experience of Croatian cytologists and gynecologists. It was presented and accepted by Croatian clinical cytologists at the Croatian Society of Clinical Cytology Convention held on December 12, 2016 in Zagreb. The main modifications relative to the Zagreb 2002 classification refer to the following: classification of ‘koilocytosis’, i.e. cytomorphological lesions associated with human papillomavirus, into the category of low-grade squamous intraepithelial lesions (LSIL); classification of ‘atypical glandular cells – probably reactive lesions’ into the category of non-neoplastic lesions; and the introduction of ‘atypical glandular cells – not othervise specified’ (AGC-NOS) into the category of abnormal glandular cells. In addition, the finding of endometrial cells in women aged ≥45 and absence of the transformation zone elements is highlighted

Zagreb 2016 classification of cervical cytology findings – modification of Zagreb 2002 and NCI Bethesda System 2014 classifications

The objective of the Zagreb 2016 classification as the third modification of the unique classification of cervical cytology findings based on the previous Zagreb 2002 and the latest Bethesda 2014 classifications is standardization of cervical cytology findings for the whole Croatia, according to the latest concepts on the biologic behavior of cervical cancer and its precursors. Besides cytomorphological lesions, Zagreb 2016 includes recommendations for diagnostic therapeutic procedures in line with the international recommendations and the experience of Croatian cytologists and gynecologists. It was presented and accepted by Croatian clinical cytologists at the Croatian Society of Clinical Cytology Convention held on December 12, 2016 in Zagreb. The main modifications relative to the Zagreb 2002 classification refer to the following: classification of ‘koilocytosis’, i.e. cytomorphological lesions associated with human papillomavirus, into the category of low-grade squamous intraepithelial lesions (LSIL); classification of ‘atypical glandular cells – probably reactive lesions’ into the category of non-neoplastic lesions; and the introduction of ‘atypical glandular cells – not othervise specified’ (AGC-NOS) into the category of abnormal glandular cells. In addition, the finding of endometrial cells in women aged ≥45 and absence of the transformation zone elements is highlighted

Cervical Cytology and HPV Test in Follow-up after Conisation or LLETZ

The patients treated with conservative surgical therapy for cervical intraepithelial neoplasia (CIN) have an increased risk to develop invasive cervical carcinoma compared to the general population. Cervical cytology and HPV test are included in the protocols for the detection of treatment failure. The purpose of the study was to analyse cytology-histology correlation after conisation or Large Loop Excision of the Transformation Zone (LLETZ), resection margin status, compliance to the follow-up protocol and evaluation of cervical cytology and HPV testing in two year period after surgical treatment. We retrospectively reviewed 251 cases of conisation or LLETZ performed between January and December, 2006. Conventional cervical smears were analysed and abnormal cytology was defined as atypical squamous cells of undetermined significance or worse (ASCUS+). The digene Hybrid capture 2 test was used for detection of high-risk HPV types. Histology analysis demonstrated CIN1+ lesion in 234 cases (93.2%) with cytology-histology correlation in 97.9% of cases. A preoperative HPV test was made in 142 histologically confirmed CIN1+ lesions and 137 (96.5%) tested positive. The resection margins were involved in 48 (20.8%) cases. In 24 (10.3%) cases the margins were difficult to determine. Abnormal cytology was found in 33 (15.2%) cases of the 217 (86.5%) patients that attended the post-treatment visits. The post-treatment HPV test was performed on 159 women and it was positive in 25 (15.7%) cases. The complete follow-up control cytology, with at least three Pap smears in the subsequent two years or with second treatment, was registered in only 146 (58.2%) patients. 14/217 (6.5%) patients underwent second treatment with histologically confirmed treatment failure. In all patients with control smear, repeated cytology found HSIL. On six women, the control HPV test was performed. In five cases, it was positive and in one case with histological diagnoses of VAIN2, it was negative. Our study confirms the important role of cervical cytology in the diagnosis of cervical intraepithelial lesions and monitoring after treatment. In the future we will have to improve compliance to the follow-up protocols and use of the HPV test in the selection of women at risk of treatment failure

Evaluation of the HPV L1 Capsid Protein in Prognosis of Mild and Moderate Dysplasia of the Cervix Uteri

Cervical intraepithelial neoplasia (CIN) can be detected in the cytologic smears years before invasive squamous cancer arises, but no reproducible morphologic criteria exist to predict behavior of cervical lesions. The possibility of predicting the clinical course of cervical lesions could be of high value in clinical practice and some women will spare of unnecessary treatment. HPV L1 capsid protein represents about 90% of the total protein on the surface of the virus and can be detected in mild to moderate dysplasia and rarely in severe dysplasia. The purpose of the study was to evaluate the use of immunodetection of HPV L1 protein on archival Pap smears with findings of mild and moderate dysplasia in predicting its clinical course. Immunochemical analyses with L1 antibody revealed positively stained nuclei of squamous epithelial cells in 56 of 114 smears (49.1%). The staining results were correlated with follow-up smears or with histologic verification. Regression (negativisation of the Pap smear for 24 months or longer) was noticed in 31 of 56 (55.4%) L1-positive cases and in 20 of 58 (34.5%) L1-negative cases. Persistent disease occured in 13 (23.2%) L1-positive cases and in 14 (24.1%) L1-negative cases. Progressive disease occured in 12 (21.4%) L1-positive cases and in 24 (41.4%) L1-negative cases. The difference in the clinical course between the L1-positive and L1-negative patients was statistically significant (p=0.025). Also, the difference in the clinical course of the L1-negative staining in the under-30 and over-30 years age group was statistically significant (p=0.04). For conclusion, our data confirm that immunostaining for HPV L1 capsid protein could offer prognostic information about mild and moderate intraepithelial cervical squamous lesions

Evaluation of the HPV L1 Capsid Protein in Prognosis of Mild and Moderate Dysplasia of the Cervix Uteri

Cervical intraepithelial neoplasia (CIN) can be detected in the cytologic smears years before invasive squamous cancer arises, but no reproducible morphologic criteria exist to predict behavior of cervical lesions. The possibility of predicting the clinical course of cervical lesions could be of high value in clinical practice and some women will spare of unnecessary treatment. HPV L1 capsid protein represents about 90% of the total protein on the surface of the virus and can be detected in mild to moderate dysplasia and rarely in severe dysplasia. The purpose of the study was to evaluate the use of immunodetection of HPV L1 protein on archival Pap smears with findings of mild and moderate dysplasia in predicting its clinical course. Immunochemical analyses with L1 antibody revealed positively stained nuclei of squamous epithelial cells in 56 of 114 smears (49.1%). The staining results were correlated with follow-up smears or with histologic verification. Regression (negativisation of the Pap smear for 24 months or longer) was noticed in 31 of 56 (55.4%) L1-positive cases and in 20 of 58 (34.5%) L1-negative cases. Persistent disease occured in 13 (23.2%) L1-positive cases and in 14 (24.1%) L1-negative cases. Progressive disease occured in 12 (21.4%) L1-positive cases and in 24 (41.4%) L1-negative cases. The difference in the clinical course between the L1-positive and L1-negative patients was statistically significant (p=0.025). Also, the difference in the clinical course of the L1-negative staining in the under-30 and over-30 years age group was statistically significant (p=0.04). For conclusion, our data confirm that immunostaining for HPV L1 capsid protein could offer prognostic information about mild and moderate intraepithelial cervical squamous lesions

Villoglandular Papillary Adenocarcinoma of the Uterine Cervix with Aggressive Clinical Course – A Case Report

Villoglandular papillary adenocarcinoma (VGA) of cervix is an uncommon but well recognized histologic subtype of cervical adenocarcinoma which usually affects young women. Based on the favorable outcomes reported in most previous cases the tumor is generally considered to have an indolent clinical course with excellent prognosis. We present a case of a 22-year-old woman admitted at our Department for glandular abnormality on cervical smear and episodes of vaginal discharge. In the Pap smear, the cytological features were suspicious but not diagnostic of adenocarcinoma, therefore reported as atypical glandular cells (AGC). Histological examination confirmed VGA associated with lymphovascular space invasion. The patient underwent radical operative procedure. Intraoperative cytologic examination detected pelvic lymph nodes metastasis. The patient was confirmed to be in an advanced stage – III B (FIGO). During a two years follow-up period a rapid dissemination of the tumor occurred and resulted with a fatal outcome. Although VGA has been reported to have a favorable prognosis, several cases with lymph node involvement have already been described. Cervical smears examination would be helpful for an early diagnosis of VGA, however the cytologic recognition is often difficult. Further investigation of the pathogenesis, diagnosis and therapy of the tumor is needed

Klasifikacija citoloških nalaza vrata maternice „Zagreb 2016“ – modifikacija klasifikacija „Zagreb 2002“ i „NCI Bethesda System 2014“

Treća modifi kacija jedinstvene klasifikacije citoloških nalaza vrata maternice „Zagreb 2016“ temeljena je na ranijoj „Zagreb 2002“ i najnovijoj „Bethesda 2014“ klasifikaciji, a u cilju standardizacije citoloških nalaza vrata maternice za cijelu Hrvatsku, prema najnovijim spoznajama o biološkom ponašanju raka vrata maternice i njegovih predstadija. „Zagreb 2016“ uključuje uz citomorfološke promjene i preporuke za dijagnostičko-terapijske postupke prema svjetskim preporukama kao i iskustvu citologa i ginekologa u Hrvatskoj, a predstavljena je i prihvaćena od kliničkih citologa Hrvatske 12. prosinca 2016. g. u Zagrebu na Stručnom sastanku Hrvatskog društva za kliničku citologiju. Glavne izmjene u odnosu na „Zagreb 2002“ odnose se na klasificiranje „koilocitoze“ odnosno citomorfoloških promjena povezanih s humanim papiloma viruom (HPV) u kategoriju skvamozne intraepitelne lezje niskog stupnja (LSIL), klasificiranje „atipičnih glandularnih stanica – vjerojatno reaktivne promjene“ u kategoriju ne-neoplastičnih promjena te uvođenje nalaza “atipične glandularne stanice – nespecificirane“ (AGC–NOS) u kategoriju abnormalnih glandularnih stanica. Osim toga, u klasifikaciji „Zagreb 2016“ poseban naglasak se daje i na nalaz endometralnih stanica kod žena nakon ≥45g., kao i na odsutnost elemenata transformacijske zone

Villoglandular Papillary Adenocarcinoma of the Uterine Cervix with Aggressive Clinical Course – A Case Report

Villoglandular papillary adenocarcinoma (VGA) of cervix is an uncommon but well recognized histologic subtype of cervical adenocarcinoma which usually affects young women. Based on the favorable outcomes reported in most previous cases the tumor is generally considered to have an indolent clinical course with excellent prognosis. We present a case of a 22-year-old woman admitted at our Department for glandular abnormality on cervical smear and episodes of vaginal discharge. In the Pap smear, the cytological features were suspicious but not diagnostic of adenocarcinoma, therefore reported as atypical glandular cells (AGC). Histological examination confirmed VGA associated with lymphovascular space invasion. The patient underwent radical operative procedure. Intraoperative cytologic examination detected pelvic lymph nodes metastasis. The patient was confirmed to be in an advanced stage – III B (FIGO). During a two years follow-up period a rapid dissemination of the tumor occurred and resulted with a fatal outcome. Although VGA has been reported to have a favorable prognosis, several cases with lymph node involvement have already been described. Cervical smears examination would be helpful for an early diagnosis of VGA, however the cytologic recognition is often difficult. Further investigation of the pathogenesis, diagnosis and therapy of the tumor is needed

Klasifikacija citoloških nalaza vrata maternice „Zagreb 2016“ – modifikacija klasifikacija „Zagreb 2002“ i „NCI Bethesda System 2014“

Treća modifi kacija jedinstvene klasifikacije citoloških nalaza vrata maternice „Zagreb 2016“ temeljena je na ranijoj „Zagreb 2002“ i najnovijoj „Bethesda 2014“ klasifikaciji, a u cilju standardizacije citoloških nalaza vrata maternice za cijelu Hrvatsku, prema najnovijim spoznajama o biološkom ponašanju raka vrata maternice i njegovih predstadija. „Zagreb 2016“ uključuje uz citomorfološke promjene i preporuke za dijagnostičko-terapijske postupke prema svjetskim preporukama kao i iskustvu citologa i ginekologa u Hrvatskoj, a predstavljena je i prihvaćena od kliničkih citologa Hrvatske 12. prosinca 2016. g. u Zagrebu na Stručnom sastanku Hrvatskog društva za kliničku citologiju. Glavne izmjene u odnosu na „Zagreb 2002“ odnose se na klasificiranje „koilocitoze“ odnosno citomorfoloških promjena povezanih s humanim papiloma viruom (HPV) u kategoriju skvamozne intraepitelne lezje niskog stupnja (LSIL), klasificiranje „atipičnih glandularnih stanica – vjerojatno reaktivne promjene“ u kategoriju ne-neoplastičnih promjena te uvođenje nalaza “atipične glandularne stanice – nespecificirane“ (AGC–NOS) u kategoriju abnormalnih glandularnih stanica. Osim toga, u klasifikaciji „Zagreb 2016“ poseban naglasak se daje i na nalaz endometralnih stanica kod žena nakon ≥45g., kao i na odsutnost elemenata transformacijske zone