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1. Prevalence of Carcinogenic Genotypes of HPV-Infected Women in a Ten-Year Period (2014–2023) in Vojvodina, Serbia

Author

Natasa Nikolic, Branka Basica, Mirjana Strbac, Lidija Terzic, Aleksandra Patic, Gordana Kovacevic, Radmila Velicki, Dusan Petrovic, Aljosa Mandic, and Vladimir Petrovic

Subjects
HPV, prevalence, genotype distribution, cervical intraepithelial lesion, Serbia, Medicine (General), R5-920
Abstract

Background and Objectives: Human papillomavirus (HPV) infection and its etiological role in the development of cervical cancer are well established. The cervical cancer mortality rate in Serbia is one of the highest among European countries, and this cancer is the second-leading cause of death in Serbian women aged from 15 to 44. Materials and Methods: This retrospective study was conducted at the Institute of Public Health of Vojvodina. A total of 10,062 cervical specimens from Serbian women were collected and HPV tested in ten years. The study patients were divided into five age groups. HPV genotype testing was performed using a commercial kit to detect 14 high-risk (HR) HPV genotypes. Additionally, cervix cytology data have been available for patients tested in 2022 and 2023. Results: An overall positive rate was found in 43.3% of patients (4356/10,062). A single HPV infection (62.1%) was the main infection pattern. The most frequent HR HPV genotypes were HPV 16, 31, 52, 56, 39, and 51, comprising 62.3% of the detected genotypes, including multiple infections. A significant difference was noted in the HPV prevalence across the different age groups, with a bimodal distribution of HPV infection. The highest prevalence was recorded in the age group ≤ 30 and those after 61 years. Women diagnosed with high-grade squamous intraepithelial lesions (HSIL) were significantly older compared to others. HR HPV is the most prevalent in patients with HSIL cytological findings (76.5%). The most common type, according to age-specific distribution and cytological findings, was HR HPV 16. Conclusions: This study provides comprehensive data on HR HPV distribution among Serbian women, which can serve as a basis for subsequent monitoring of genotypic distribution. It is particularly significant considering they are missing in the updated ICO/IARC Report for Serbia, and the cervical cancer mortality rate in Serbia is one of the highest among European countries.

Published
2024
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2. E6/E7 mRNA Expression of the Most Prevalent High-Risk HPV Genotypes in Cervical Samples from Serbian Women

Author

Natasa Nikolic, Branka Basica, Aljosa Mandic, Nela Surla, Vera Gusman, Deana Medic, Tamas Petrovic, Mirjana Strbac, and Vladimir Petrovic

Subjects
E6, E7, HPV, cervical intraepithelial lesion, biomarker, Serbia, Medicine (General), R5-920
Abstract

Cervical cancer caused by persistent infection with HR HPV genotypes is the second leading cause of death in women aged 15 to 44 in Serbia. The expression of the E6 and E7 HPV oncogenes is considered as a promising biomarker in diagnosing high-grade squamous intraepithelial lesions (HSIL). This study aimed to evaluate HPV mRNA and DNA tests, compare the results according to the severity of the lesions, and assess the predictive potential for the diagnosis of HSIL. Cervical specimens were obtained at the Department of Gynecology, Community Health Centre Novi Sad, Serbia, and the Oncology Institute of Vojvodina, Serbia, during 2017–2021. The 365 samples were collected using the ThinPrep Pap test. The cytology slides were evaluated according to the Bethesda 2014 System. Using a real-time PCR test, HPV DNA was detected and genotyped, while the RT-PCR proved the presence of E6 and E7 mRNA. The most common genotypes in Serbian women are HPV 16, 31, 33, and 51. Oncogenic activity was demonstrated in 67% of HPV-positive women. A comparison of the HPV DNA and mRNA tests to assess the progression of cervical intraepithelial lesions indicated that higher specificity (89.1%) and positive predictive value (69.8–78.7%) were expressed by the E6/E7 mRNA test, while higher sensitivity was recorded when using the HPV DNA test (67.6–88%). The results determine the higher probability of detecting HPV infection by 7% provided by the mRNA test. The detected E6/E7 mRNA HR HPVs have a predictive potential in assessing the diagnosis of HSIL. The oncogenic activity of HPV 16 and age were the risk factors with the strongest predictive values for the development of HSIL.

Published
2023
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3. SUCCOR Nodes: May Sentinel Node Biopsy Determine the Need for Adjuvant Treatment?

Author

Arantxa Berasaluce Gómez MD, Nerea Martín-Calvo MD, Félix Boria MD, Nabil Manzour MD, Enrique Chacón MD, Nicolò Bizzarri MD, Luis Chiva MD, Alejandra, Martinez, Alfonso, Quesada, Ali, Kucukmetin, Alicia, Vázquez, Aljosa, Mandic, Andrea, Casajuana, Andreas, Kavallaris, Anna, Fagotti, Anna, Perrone, Annamaria, Ferrero, Arantxa, Lekuona, Arno, Uppin, Artem, Stepanyan, Benito, Chiofalo, Bibiana, Morillas, Carmen, Tauste, Claudia, Andrade, Constantijne, Mom, Cosima, Brucker, Cosmin-Paul, Sarac, Daniel, Vázquez-Vicente, David, Cibula, Denis, Querleu, Diego, Erasun, Dilyara, Kaidarova, Dimitrios, Tsolakidis, Dimitros, Haidopoulos, Dmytro, Golub, Eduard-Aexandru, Bonci, Elif, Aksahin, Elisabete, Gonçalves, Enrique, Moratalla, Erbil, Karaman, Eva, Myriokefalitaki, Fabio, Ghezzi, Fabrice, Narducci, Fernando, Roldan, Francesco, Raspagliesi, Frédéric, Goffin, Frederic, Grandjean, Frédéric, Guyon, Fuat, Demirkiran, Gabriel, Fiol, Galina, Chakalova, Gemma, Mancebo, George, Vorgias, Gerhard, Gebauer, Gesine, Meili, Gines, Hernandez-Cortes, Giorgio, Bogani, Gloria, Cordeiro, Goran, Vujić, Gustavo, Mendinhos, Hans, Trum, Hélène, Bonsang-Kitzis, Herman, Haller, Ignace, Vergote, Ignacio, Zapardiel, Igor, Aluloski, Igor, Berlev, Imre, Pete, Ioannis, Kalogiannidis, Ioannis, Kotsopoulos, Iryna, Yezhova, Javier, Díez, Feron, Jean G., Jens-Peter, Scharf, Jogchum, Beltman, Jolien, Haesen, Jordi, Ponce, Jorge, Cea, Jose Ángel Mínguez, José, García, Juan, Arévalo-Serrano, Juan, Gilabert, Juan Luis Alcazar, Kersti, Kukk, Khadra, Galaal, Laura, Cárdenas, Laurentiu, Pirtea, Mereu, Liliana, Luigi Pedone Anchora, Lukas, Dostalek, Lukasz, Klasa, Maja, Pakižimre, Manuela, Undurraga, Marcin, Jedryka, Margarida, Bernardino, Maria, Alonso-Espias, María Belén Martín-Salamanca, Maria, Cuadra, Mariana, Tavares, Mario, Malzoni, Mathias, Fehr, Mathieu, Luyckx, Maximilian, Lanner, Meelis, Leht, Mehmet, Meydanli, Michael, Mallmann, Mihai, Căpîlna, Mikulás, Redecha, Milena, Mitrovic, Maenpaa, Minna M., Miriam, Guijarro, Nabil, Abdalla, Nana, Gomes, Natalia, Povolotskaya, Nikola, Badzakov, Octavio, Arencibia, Özgür, Akbayir, Pere, Cavalle, Petra, Zusterzeel, Philip, Rolland, Pluvio, Coronado, Rasiah, Bharathan, Reeli, Saaron, Rita, Sousa, Robert, Fruscio, Robert, Jach, Robert, Poka, Rosa, Barrachina, Santiago, Domingo, Sara, Morales, Sedat, Akgöl, Sergi, Fernandez-Gonzalez, Shamistan, Aliyev, Sofía, Herrero, Soledad, Fidalgo, Sonia, Prader, Špela, Smrkolj, Stamatios, Petousis, Stefan, Kovachev, Taner, Turan, Tayfun, Toptas, Teresa, Castellanos, Teresa Diniz da Costa, Tiermes, Marina, Vanna, Zanagnolo, Victor, Martin, Virginia, Gonzalez, Vladimír Študent &amp, and Vladyslav, Sukhin

Published
2023

4. SUCCOR Risk: Design and Validation of a Recurrence Prediction Index for Early-Stage Cervical Cancer

Author

Manzour, Nabil, Chiva, Luis, Chacón, Enrique, Martin-Calvo, Nerea, Boria, Felix, Minguez, José A, Alcazar, Juan, L, Vanna, Zanagnolo, Denis, Querleu, Mihai, Căpîlna, Anna, Fagotti, Ali, Kucukmetin, Constantijne, Mom, Galina, Chakalova, Shamistan, Aliyev, Mario, Malzoni, Fabrice, Narducci, Octavio, Arencibia, Francesci, Raspagliesi, Tayfun, Toptas, David, Cibula, Dilyara, Kaidarova, Mehmet, Meydanli, Mariana, Tavares, Dmytro, Golub, Anna, Perrone, Robert, Poka, Dimitrios, Tsolakidis, Goran, Vujić, Marcin, Jedryka, Petra, Zusterzeel, Jogchum, Beltman, Frédéric, Goffin, Dimitros, Haidopoulos, Herman, Haller, Robert, Jach, Iryna, Yezhova, Igor, Berlev, Margarida, Bernardino, Rasiah, Bharathan, Maximilian, Lanner, Vladyslav, Sukhin, Jean, G Feron, Robert, Fruscio, Kersti, Kukk, Jordi, Ponce, Nabil, Abdalla, Özgür, Akbayir, Sedat, Akgöl, Elif, Aksahin, Maria, Alonso-Espias, Igor, Aluloski, Claudia, Andrade, Nikola, Badzakov, Rosa, Barrachina, Giorgio, Bogani, Eduard-Aexandru, Bonci, Hélène, Bonsang-Kitzis, Cosima, Brucker, Laura, Cárdenas, Andrea, Casajuana, Pere, Cavalle, Jorge, Cea, Benito, Chiofalo, Gloria, Cordeiro, Pluvio, Coronado, Maria, Cuadra, Javier, Díez, Teresa Diniz da Costa, Santiago, Domingo, Lukas, Dostalek, Fuat, Demirkiran, Diego, Erasun, Mathias, Fehr, Sergi, Fernandez-Gonzalez, Soledad, Fidalgo, Gabriel, Fiol, Khadra, Galaal, José, García, Gerhard, Gebauer, Fabio, Ghezzi, Juan, Gilabert, Nana, Gomes, Elisabete, Gonçalves, Virginia, Gonzalez, Frederic, Grandjean, Miriam, Guijarro, Frédéric, Guyon, Jolien, Haesen, Gines, Hernandez-Cortes, Sofía, Herrero, Imre, Pete, Ioannis, Kalogiannidis, Erbil, Karaman, Andreas, Kavallaris, Lukasz, Klasa, Ioannis, Kotsopoulos, Stefan, Kovachev, Meelis, Leht, Arantxa, Lekuona, Mathieu, Luyckx, Michael, Mallmann, Gemma, Mancebo, Aljosa, Mandic, Tiermes, Marina, Victor, Martin, María Belén Martín-Salamanca, Alejandra, Martinez, Gesine, Meili, Gustavo, Mendinhos, Mereu, Liliana, Milena, Mitrovic, Sara, Morales, Enrique, Moratalla, Bibiana, Morillas, Eva, Myriokefalitaki, Maja, Pakižimre, Stamatios, Petousis, Laurentiu, Pirtea, Natalia, Povolotskaya, Sonia, Prader, Alfonso, Quesada, Mikuláš, Redecha, Fernando, Roldan, Philip, Rolland, Reeli, Saaron, Cosmin-Paul, Sarac, Jens-Peter, Scharf, Špela, Smrkolj, Rita, Sousa, Artem, Stepanyan, Vladimír, Študent, Carmen, Tauste, Hans, Trum, Taner, Turan, Manuela, Undurraga, Arno, Uppin, Alicia, Vázquez, Ignace, Vergote, George, Vorgias, Ignacio, Zapardiel, Amsterdam Reproduction & Development (AR&D), Obstetrics and gynaecology, CCA - Imaging and biomarkers, Manzour, N, Chiva, L, Chacon, E, Martin-Calvo, N, Boria, F, Minguez, J, Alcazar, J, Zanagnolo, V, Querleu, D, Capilna, M, Fagotti, A, Kucukmetin, A, Mom, C, Chakalova, G, Aliyev, S, Malzoni, M, Narducci, F, Arencibia, O, Raspagliesi, F, Toptas, T, Cibula, D, Kaidarova, D, Meydanli, M, Tavares, M, Golub, D, Perrone, A, Poka, R, Tsolakidis, D, Vujic, G, Jedryka, M, Zusterzeel, P, Beltman, J, Goffin, F, Haidopoulos, D, Haller, H, Jach, R, Yezhova, I, Berlev, I, Bernardino, M, Bharathan, R, Lanner, M, Sukhin, V, Feron, J, Fruscio, R, Kukk, K, Ponce, J, Abdalla, N, Akbayir, O, Akgol, S, Aksahin, E, Alonso-Espias, M, Aluloski, I, Andrade, C, Badzakov, N, Barrachina, R, Bogani, G, Bonci, E, Bonsang-Kitzis, H, Brucker, C, Cardenas, L, Casajuana, A, Cavalle, P, Cea, J, Chiofalo, B, Cordeiro, G, Coronado, P, Cuadra, M, Diez, J, da Costa, T, Domingo, S, Dostalek, L, Demirkiran, F, Erasun, D, Fehr, M, Fernandez-Gonzalez, S, Fidalgo, S, Fiol, G, Galaal, K, Garcia, J, Gebauer, G, Ghezzi, F, Gilabert, J, Gomes, N, Goncalves, E, Gonzalez, V, Grandjean, F, Guijarro, M, Guyon, F, Haesen, J, Hernandez-Cortes, G, Herrero, S, Pete, I, Kalogiannidis, I, Karaman, E, Kavallaris, A, Klasa, L, Kotsopoulos, I, Kovachev, S, Leht, M, Lekuona, A, Luyckx, M, Mallmann, M, Mancebo, G, Mandic, A, Marina, T, Martin, V, Martin-Salamanca, M, Martinez, A, Meili, G, Mendinhos, G, Mereu, L, Mitrovic, M, Morales, S, Moratalla, E, Morillas, B, Myriokefalitaki, E, Pakizimre, M, Petousis, S, Pirtea, L, Povolotskaya, N, Prader, S, Quesada, A, Redecha, M, Roldan, F, Rolland, P, Saaron, R, Sarac, C, Scharf, J, Smrkolj, S, Sousa, R, Stepanyan, A, Student, V, Tauste, C, Trum, H, Turan, T, Undurraga, M, Uppin, A, Vazquez, A, Vergote, I, Vorgias, G, and Zapardiel, I

Subjects
cervical cancer, Cevical cancer, Uterine Cervical Neoplasms, Hysterectomy, Prognosis, Risk Assessment, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], conization, Settore MED/40 - GINECOLOGIA E OSTETRICIA, Oncology, Recurrence, radical hysterectomy, Humans, Female, Surgery, Neoplasm Recurrence, Local, Neoplasm Staging, Retrospective Studies
Abstract

Objective Based on the SUCCOR study database, our primary objective was to identify the independent clinical pathological variables associated with the risk of relapse in patients with stage IB1 cervical cancer who underwent a radical hysterectomy. Our secondary goal was to design and validate a risk predictive index (RPI) for classifying patients depending on the risk of recurrence. Methods Overall, 1116 women were included from January 2013 to December 2014. We randomly divided our sample into two cohorts: discovery and validation cohorts. The test group was used to identify the independent variables associated with relapse, and with these variables, we designed our RPI. The index was applied to calculate a relapse risk score for each participant in the validation group. Results A previous cone biopsy was the most significant independent variable that lowered the rate of relapse (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.17–0.60). Additionally, patients with a tumor diameter >2 cm on preoperative imaging assessment (OR 2.15, 95% CI 1.33–3.5) and operated by the minimally invasive approach (OR 1.61, 95% CI 1.00–2.57) were more likely to have a recurrence. Based on these findings, patients in the validation cohort were classified according to the RPI of low, medium, or high risk of relapse, with rates of 3.4%, 9.8%, and 21.3% observed in each group, respectively. With a median follow-up of 58 months, the 5-year disease-free survival rates were 97.2% for the low-risk group, 88.0% for the medium-risk group, and 80.5% for the high-risk group (p < 0.001). Conclusion Previous conization to radical hysterectomy was the most powerful protective variable of relapse. Our risk predictor index was validated to identify patients at risk of recurrence.

Published
2022
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5. Association of Peritoneal Cytology with Other Prognostic Factors in Endometrial Cancer

Author

Slobodan Maricic, Aljosa Mandic, Tijana Vasiljević, Bojana Gutic, Nemanja Stevanovic, and Tamara Maksimovic

Subjects
Histology, Pathology and Forensic Medicine
Abstract

It is still debatable whether surgical staging of endometrial cancer (EC) should include sampling of peritoneal cytology (PC) and for what purpose this should be done. The aim of our study was to determine the significance of peritoneal cytology in EC and its association with other histological and clinical parameters.This is a retrospective study that comprises of results from 357 patients with EC that were operated in our center in the previous nine years. Patients were divided into two groups: the first group with a positive and the second group with a negative PC.Malignant cells were found in the peritoneal cytology of 23 patients (6.4%), while 334 patients (93.6%) had negative PC. There was no significant difference in patients' age between the two groups (Malignant peritoneal cytology is associated with other negative prognostic factors in endometrial cancer (histological grade, FIGO stage, and non-endometrioid histological subtypes). Based on these findings, we encourage sampling of peritoneal washing in all EC patients and consider it mandatory in patients with non-endometrioid subtype, high-grade histology, and in advanced FIGO stage.

Published
2022

6. Preliminary outcomes of five-year survival for ovarian malignancies in profiled Serbian Oncology Centre

Author

Bojana Gutic, Tatjana Bozanovic, Aljosa Mandic, Stefan Dugalic, Jovana Todorovic, Miroslava Gojnic Dugalic, Demet Sengul, Dzenana A. Detanac, Ilker Sengul, Dzemail Detanac, Tugrul Kesicioglu, and José Maria Soares Junior

Subjects
Oncology, Ovary, Carcinoma, Pathology, Histopathology, Surgery, General Medicine
Abstract

Objective: The present study purposed to determine characteristics of ovarian carcinoma and to analyze predictors of survival in patients with ovarian carcinoma. Method: A retrospective cohort study was conducted including the patients with diagnosed ovarian carcinoma treated at the Clinic for Operative Oncology, Oncology Institute of Vojvodina in the period from January 2012 to December 2016. Seventy-two women with ovarian carcinoma were included in the analysis. The data about the histological type of tumor, disease stage, treatment, lymphatic infiltration, and surgical procedure were collected retrospectively, using the database of the institution where the research was conducted (BirPis 21 SRC Infonet DOO – Information System Oncology Institute of Vojvodina). Descriptive statistics and multivariate analysis using Cox proportional hazards model were performed. Results: The univariate Cox regression analysis identified histology, tumor grade, FIGO (International Federation of Gynecology and Obstetrics) stage, NACT (Neoadjuvant Chemotherapy), number of therapy cycles, type of surgery, and chemotherapy response as independent predictors of mortality. Finally, the type of tumor and chemotherapy response had an increased hazard ratio for mortality in the multivariate Cox regression model. Herewith, the percentage of high-grade, advanced-stage ovarian cancer patients with complete response to chemotherapy, absence of recurrent disease, and lymphovascular space invasion were significant predictors of survival in patients with ovarian carcinoma. Conclusions: Herein, emerging data regarding precision medicine and molecular-based personalized treatments are promising and will likely modify the way the authors provide multiple lines of treatments in the near future.

Published
2023
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