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Giants in Obstetrics and Gynecology Series: a profile of Zoltán Papp, MD, PhD, DSc, FACOG (Hon)

  • Roberto Romero
    Correspondence
    Corresponding author: Roberto Romero, MD, DMedSci.
    Affiliations
    Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Detroit, MI
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Published:October 01, 2022DOI:https://doi.org/10.1016/j.ajog.2022.07.042
      Zoltán Papp, MD, PhD, DSc, FACOG (Hon) is a pioneer in the fields of obstetrics and gynecology and of human genetics. Regarded as larger-than-life among his peers, he is a physician polymath equally at home reviewing karyotypes and fetal ultrasound images as performing nerve-sparing radical hysterectomies for cervical cancer. He is the eighth successor to Ignaz Semmelweis as Professor and Director of the First Department of Obstetrics and Gynecology in the medical school at Semmelweis University in Budapest, Hungary. He has brought together human genetics and obstetrics, implemented routine screening for fetal congenital anomalies in the 1980s, described a unique genetic syndrome bearing his name—the Váradi–Papp syndrome—and has mentored and trained leaders in obstetrics and gynecology. He serves as Editor-in-Chief of the renowned Hungarian Medical Weekly (Orvosi Hetilap), where Semmelweis published his seminal work on childbed fever.
      After serving many years at Semmelweis University, Zoltán stepped down as Chair at the age of 65 to establish the Maternity Private Clinic of Obstetrics and Gynecology on the Buda side of the Danube River. The overall view of his admirers and friends was articulated by Professor Leslie Iffy: “the intellectual center of the profession moved from Pest to Buda with Zoltán.”
      For his numerous contributions, among many other accomplishments, Dr Papp is recognized as a “Giant in Obstetrics and Gynecology.”

      Early life and education

      Zoltán, born in 1942, and his two sisters—one a judge, the other a teacher—were raised and educated in Mezökövesd, a town about 80 miles northeast of Budapest. Zoltán’s father, an orphan by the age of 10, overcame the hardship with talent and diligence, instilled a work ethic in his children, and set the tone for their future achievements. After studying at universities in Budapest, Vienna, and Berlin, he became a teacher of Hungarian and German and later the headmaster of St. Laszlo High School where Zoltán and his sisters attended. After graduating high school in 1960, Zoltán entered medical school in Debrecen, Hungary’s second largest city, located in the Northern Great Plain region 50 miles east of his childhood home.
      Zoltán earned his medical degree and graduated summa cum laude from the University of Debrecen Medical School in 1966 and remained at his alma mater in the Department of Obstetrics and Gynecology for 24 years, becoming professor in 1985. He defended his PhD thesis, “Prenatal Diagnosis of Chromosome Aberrations,” before the Hungarian Academy of Sciences in 1972, and his doctorate in science (DSc) dissertation, “Prenatal Diagnosis of Neural Tube Defects,” in 1981.
      In 1971, Zoltán married Dr Valéria Váradi, who is a pediatrician and neonatologist with advanced training in anesthesiology. Zoltán and Valéria have collaborated professionally throughout their marriage, and Zoltán considers this partnership indispensable to all that he has achieved.

      Bringing medical genetics into obstetrics

      Zoltán's fascination with the study of genetics dates back to his time in medical school. He participated in the Union of Science Students at the Department of Anatomy, Histology, and Embryology, where he acquired knowledge of morphology and tissue culture that he then combined with his experience in genetics. During his residency, when genetics was not part of the curriculum in obstetrics and gynecology, he established a cytogenetics laboratory in Debrecen. His first original publication described the successful use of Barr bodies to assess fetal sex on the basis of the analysis of cells obtained at the time of midtrimester amniocentesis. This article was published in Orvosi Hetilap.
      • Papp Z.
      • Gardó S.
      • Herpay G.
      • Árvay S.
      [Prenatal sex determination].
      The accuracy of sex determination was such that Zoltán concluded that the method could be recommended for prenatal sex determination in X-linked diseases.
      • Papp Z.
      • Gardó S.
      • Herpay G.
      • Árvay A.
      Prenatal sex determination by amniocentesis.
      Subsequently, he reported on lymphocyte culture derived from umbilical cord blood for karyotype determination, an article published in The Lancet.
      • Papp Z.
      • Gardó S.
      Cytogenetic analysis of cord-blood lymphocytes.
      Zoltán mastered the reading of karyotypes and used this technique to identify aneuploidy and fetal sex for the prevention of Duchenne muscular dystrophy and hemophilia. He then extended his studies to translocation carriers and cases of parental trisomy mosaicism.
      • Gardó S.
      • Papp Z.
      • Gaál J.
      XO-XX mosaicism in the Rokitansky-Kuster-Hauser syndrome.
      • Papp Z.
      • Gardó S.
      • Árvay A.
      [Indications for prenatal cytogenetic examination].
      • Papp Z.
      • Csécsei K.
      • Skapinyecz J.
      • Dolhay B.
      Paternal normal-trisomy 21 mosaicism as an indication for amniocentesis.
      • Papp Z.
      • Dolhay B.
      • Gardó S.
      Familial 21/22 translocation.
      In 1971, just five days after their wedding, Zoltán and Valéria traveled to Paris to attend the Fourth World Congress of Human Genetics, where he presented a case of the prenatal diagnosis of unbalanced G/G translocation Down syndrome.
      • Papp Z.
      • Gardó S.
      • Méhes K.
      [Intrauterine diagnosis of G-G translocation].
      He also reported that balanced translocations occur frequently in couples with recurring miscarriages.
      • Papp Z.
      • Gardó S.
      • Dolhay B.
      Chromosome study of couples with repeated spontaneous abortions.
      His contributions to prenatal diagnosis were seminal in Hungary and throughout Europe. Zoltán made clinical genetics a compulsory subject at the University of Debrecen Medical School and placed Hungary at the forefront of a new discipline in obstetrics and gynecology—prenatal genetic diagnosis.

      Introducing the screening of fetal congenital anomalies with ultrasound

      In 1978, Zoltán spent one year in Scotland as a Wellcome Research Fellow (Figure 1). To refine his clinical cytogenetic skills, he studied at the University of Edinburgh in the Medical Research Council Unit headed by Dr John H. Evans—where Zoltán met Dr Ian Donald, the pioneer of obstetrical ultrasound, in the Western General Hospital. Zoltán immediately recognized the potential of ultrasound imaging for the delineation of fetal anatomy and the value of this technique for the detection of anatomic congenital anomalies. Zoltán spent every free moment at the ultrasound laboratory and developed an interest in central nervous system disorders, and, in particular, spina bifida. He also implemented immune-cytochemical tests for the detection of neural tube defects, (eg, phagocyte-like macrophages in amniotic fluid).
      • Papp Z.
      • Bell J.E.
      Uncultured cells in amniotic fluid from normal and abnormal foetuses.
      • Polgár K.
      • Sipka S.
      • Ábel G.
      • Papp Z.
      Neutral-red uptake by amniotic-fluid macrophages in neural-tube defects: a rapid test.
      • Polgár K.
      • Ábel G.
      • Laczkó J.
      • Sipka S.
      • Papp Z.
      Immunocytochemical characterization of amniotic fluid macrophages in cases of fetal neural tube defects.
      • Polgár K.
      • Ádány R.
      • Ábel G.
      • Kappelmayer J.
      • Muszbek L.
      • Papp Z.
      Characterization of rapidly adhering amniotic fluid cells by combined immunofluorescence and phagocytosis assays.
      Returning home, he reported on a wide range of fetal anomalies diagnosed by prenatal ultrasound
      • Tóth Z.
      • Vachter J.
      • Szeifert G.
      • et al.
      Antenatally diagnosed thanatophoric dysplasia.
      • Tóth Z.
      • Kóródi I.
      • Vachter J.
      • Dezsö B.
      • Papp Z.
      Antenatally diagnosed hygroma colli.
      • Szabó M.
      • Varga P.
      • Zalatnai A.
      • Hidvégi J.
      • Tóth Z.
      • Papp Z.
      Sacrococcygeal teratoma and normal alphafetoprotein concentration in amniotic fluid.
      • Szeifert G.
      • Csécsei K.
      • Tóth Z.
      • Papp Z.
      Prenatal diagnosis of ascites caused by cytomegalovirus hepatitis.
      • Papp Z.
      • Csécsei K.
      • Tóth Z.
      • Polgár K.
      • Szeifert G.T.
      Exencephaly in human fetuses.
      • Tóth Z.
      • Csécsei K.
      • Szeifert G.
      • Török O.
      • Papp Z.
      Early prenatal diagnosis of cyclopia associated with holoprosencephaly.
      • Mórocz I.
      • Szeifert G.T.
      • Molnár P.
      • Tóth Z.
      • Csécsei K.
      • Papp Z.
      Prenatal diagnosis and pathoanatomy of iniencephaly.
      • Csécsei K.
      • Kovács T.
      • Hinchliffe S.A.
      • Papp Z.
      Incidence and associations of single umbilical artery in prenatally diagnosed malformed, midtrimester fetuses: a review of 62 cases.
      • Török O.
      • Tóth Z.
      • Szeifert G.T.
      • Papp Z.
      Prenatal diagnosis and management of chondrodysplasias.
      • Görbe É.
      • Hajdú J.
      • Verebély T.
      • Papp Z.
      Congenital diaphragmatic hernia: can prenatal ultrasonography predict outcome?.
      • Csabay L.
      • Szabó I.
      • Papp C.
      • Tóth-Pál E.
      • Papp Z.
      Central nervous system anomalies.
      and insisted on the importance of correlation with autopsy findings establishing fetopathology and fetal dysmorphology.
      • Papp Z.
      Post-termination dysmorphological studies and genetic counseling.
      ,
      • Papp Z.
      The Semmelweis University experience.
      Figure thumbnail gr1
      Figure 1Zoltán Papp and Valéria Váradi in Scotland, 1978
      Thanks to scholarships awarded by the Wellcome Trust, Zoltán Papp studied and conducted research for two years in the United Kingdom, first at the University of Edinburgh, Scotland, in 1978, and again in 1984 and 1985 at the University of Oxford, England. His wife, Valéria Váradi, visited him in 1978. They enjoyed many excursions throughout Scotland. Photo courtesy of Professor Zoltán Papp.
      Romero. Giants in Obstetrics and Gynecology Series: a profile of Zoltán Papp, MD, PhD, DSc, FACOG (Hon). Am J Obstet Gynecol 2022.
      Ahead of his time, Zoltán introduced routine ultrasound examination of low-risk patients to screen for congenital anomalies in the early 1980s in Hungary. Over a three-year span, Zoltán’s team screened 63,000 pregnant women and concluded that the combination of ultrasound and maternal serum alpha-fetoprotein could detect 63% of major anatomic anomalies with 100% specificity and 100% positive predictive value (excluding cardiac anomalies). Moreover, he reported that the sensitivity of an ultrasound at 18 weeks of gestation was higher than that of the maternal serum alpha-fetoprotein screening.
      • Papp Z.
      The Semmelweis University experience.
      • Tóth-Pál E.
      • Papp C.
      • Papp Z.
      Computer follow-up system for obstetric, genetic and neonatal care in Hungary.
      • Tóth-Pál E.
      • Papp C.
      • Papp Z.
      Quality and quantity ratios of obstetric care in the gypsy and non-gypsy population in Hungary.
      • Papp Z.
      • Tóth-Pál E.
      • Papp C.
      • et al.
      Impact of prenatal mid-trimester screening on the prevalence of fetal structural anomalies: a prospective epidemiological study.
      • Szabó M.
      • Veress L.
      • Münnich Á.
      • Papp Z.
      Maternal age-dependent and sex-related changes of gestational serum alpha-fetoprotein.
      This successful detection of anomalies with ultrasound in Hungary had an important effect on the organization of prenatal care.

      Prenatal molecular diagnosis

      Zoltán spent a second year as a Wellcome Research Fellow in 1984 and 1985, this time at the Churchill Hospital and John Radcliffe Maternity Hospital at Oxford University, focusing on molecular genetics and prenatal diagnosis. On his return to Hungary, he organized the DNA testing of chorionic villus samples
      • Bolodár A.
      • Horváth K.
      • Németi M.
      • Papp Z.
      First trimester chorionic villus sampling for DNA analysis.
      ,
      • Than N.G.
      • Papp Z.
      Ethical issues in genetic counseling.
      and investigated the prenatal diagnosis of cystic fibrosis.
      • Németi M.
      • Louie E.
      • Papp Z.
      • Johnson J.P.
      Molecular analysis of cystic fibrosis in the Hungarian population.
      ,
      • Németi M.
      • Johnson J.P.
      • Papp Z.
      • Louie E.
      The occurrence of various non-delta F508 CFTR gene mutations among Hungarian cystic fibrosis patients.
      Zoltán also introduced the fluorescent polymerase chain reaction method for prenatal screening and for preimplantation diagnosis of trisomies 21, 13, and 18 from amniotic fluid cell, chorionic villus, and blastomere samples.
      • Tóth T.
      • Findlay I.
      • Nagy B.
      • Quirke P.
      • Papp Z.
      Prenatal detection of trisomy 21 by fluorescent polymerase chain reaction: importance of primer selection and criticism of an earlier report.
      • Tóth T.
      • Findlay I.
      • Papp C.
      • et al.
      Prenatal detection of trisomy 21 and 18 from amniotic fluid by quantitative fluorescent polymerase chain reaction.
      • Tóth T.
      • Papp Z.
      • Findlay I.
      Rapid prenatal detection of aneuploidies by fluorescent polymerase chain reaction.
      • Tóth T.
      • Findlay I.
      • Papp C.
      • et al.
      Prenatal detection of trisomy 13 from amniotic fluid by quantitative fluorescent polymerase chain reaction.
      • Findlay I.
      • Matthews P.
      • Tóth T.
      • Quirke P.
      • Papp Z.
      Same day diagnosis of Down’s syndrome and sex in single cells using multiplex fluorescent PCR.
      • Findlay I.
      • Tóth T.
      • Matthews P.
      • Marton T.
      • Quirke P.
      • Papp Z.
      Rapid determination of trisomy 18 parental origin using fluorescent PCR and small tandem repeat markers: case reports.
      • Findlay I.
      • Tóth T.
      • Matthews P.
      • Marton T.
      • Quirke P.
      • Papp Z.
      Rapid trisomy diagnosis (21, 18, and 13) using fluorescent PCR and short tandem repeats: applications for prenatal diagnosis and preimplantation genetic diagnosis.
      This time, he used molecular methods to access the genetic basis of colon polyposis,
      • Tóth T.
      • Kristóf T.
      • Ujszászy L.
      • Gerö G.
      • Nagy B.
      • Papp Z.
      Presymptomatic diagnosis of familial colon polyposis.
      Huntington’s chorea,
      • Tóth T.
      • Németi M.
      • Papp Z.
      Detection of CAG repeats using silver staining in patients with Huntington disease in Hungary.
      • Tóth T.
      • Papp C.
      • Németi M.
      • Papp Z.
      Questions and problems in direct predictive testing for Huntington’s disease.
      • Tóth T.
      • Nagy B.
      • Papp Z.
      PCR reagents for detection of (CAG)n repeats in Huntington disease.
      • Tóth T.
      • Findlay I.
      • Nagy B.
      • Papp Z.
      Accurate sizing of (CAG)n repeats causing Huntington disease by fluorescent PCR.
      Ivemark syndrome,
      • Tóth T.
      • Hajdú J.
      • Marton T.
      • Nagy B.
      • Papp Z.
      Connexin43 gene mutations and heterotaxy.
      Pearson syndrome,
      • Tóth T.
      • Bókay J.
      • Szönyi L.
      • Nagy B.
      • Papp Z.
      Detection of mtDNA deletion in Pearson syndrome by two independent PCR assays from Guthrie card.
      and noninvasive fetal RhD genotype in maternal blood.
      • Tóth T.
      • Papp C.
      • Tóth-Pál E.
      • Nagy B.
      • Papp Z.
      Fetal RhD genotyping by analysis of maternal blood. A case report.

      The Váradi–Papp syndrome

      Zoltán and Valéria discovered a group of consanguineous Hungarian Romani individuals diagnosed to have a cluster of defects, which included holoprosencephaly, oral malformations (cleft lip or palate or lingual nodule), and digital malformations (reduplication of the big toes and supernumerary fingers). These features overlapped with several syndromes, in particular, trisomy 13. After implementing cytogenetics to exclude this aneuploidy, Zoltán and Valéria realized this was a new entity, named the Váradi–Papp syndrome, also known as the orofaciodigital syndrome type-VI.
      • Váradi V.
      • Szabó L.
      • Papp Z.
      Syndrome of polydactyly, cleft lip/palate or lingual lump, and psychomotor retardation in endogamic gypsies.
      This autosomal-recessive disorder can be diagnosed with ultrasound in the midtrimester, as reported by Zoltán and Valéria, and is included in McKusick’s Mendelian Inheritance in Man (#277170).
      • McKusick V.A.
      277170 Váradi-Papp syndrome (polydactyly, cleft lip/palate or lingual lump, psychomotor retardation; orofaciodigital syndrome VI).
      They also have chronicled and published 25 years of study of this syndrome.
      • Váradi V.
      • Papp Z.
      [25 years’ history of Váradi-Papp syndrome (orofaciodigital syndrome VI)].
      ,
      • Papp Z.
      Twenty-five years’ history of Váradi-Papp syndrome (orofaciodigital syndrome VI).

      Folic acid to reduce the rate of neural tube defects

      While at the University of Debrecen, Zoltán became intrigued by the potential role of vitamins for the prevention of neural tube defects. Given his interest in medical genetics, he was invited to join a group organized by the British Medical Research Council to study vitamins, led by Dr Nicholas Wald of the United Kingdom. These distinguished investigators reported the results of a multicenter trial conducted at 33 centers in seven countries to determine whether the administration of folic acid or a mixture of seven other vitamins around the time of conception could prevent neural tube defects. The trial was conducted in women who had a previously affected pregnancy and who were randomized to one of four groups treated with folic acid, other vitamins, and both or neither. Hungary contributed substantially to the trial, which reported a 72% reduction in neural tube defects after antenatal administration of folic acid but not of the other vitamins.
      Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group.
      This finding is the basis for the recommendation of supplementing folic acid before pregnancy, a key advance in preconceptional care.

      Successor to Ignaz Semmelweis

      In 1990, Zoltán moved to Budapest to become Chair of the Department of Obstetrics and Gynecology at Semmelweis University, a position formerly occupied by Ignaz Semmelweis (Figure 2). Here, Zoltán brought his interest in genetics and established a cytogenetic and molecular genetic laboratory and advocated strongly for clinical genetics at the Women’s Clinic. During his tenure as Professor at Semmelweis University, Zoltán achieved national and global recognition as a clinician, teacher, investigator, and leader in obstetrics and gynecology.
      Figure thumbnail gr2
      Figure 2Statue of Ignaz Semmelweis, the “Savior of Mothers,” at Semmelweis University, Budapest, Hungary
      Professor Ignaz Semmelweis altered medical history by introducing chlorinous handwashing to reduce the rate of mortality among mothers in labor presenting with puerperal, or childbed, fever. In 2002, the faculty of the Women’s Clinic at Semmelweis University, headed by Professor Zoltán Papp, the eighth successor to the Semmelweis Chair, unveiled a bronze statue resting on a marble column in the garden of the building. Every 1st of July, on Semmelweis’s birthday, the faculty lays a wreath as part of an annual ceremony honoring his genius. Photo courtesy of Professor Zoltán Papp.
      Romero. Giants in Obstetrics and Gynecology Series: a profile of Zoltán Papp, MD, PhD, DSc, FACOG (Hon). Am J Obstet Gynecol 2022.
      Zoltán founded the Hungarian Society of Ultrasound in Obstetrics and Gynecology in 1992 and introduced a quality assurance and certification program, which required annual testing of obstetricians, gynecologists, and technical personnel who were issued certificates after fulfilling licensure requirements.
      • Papp Z.
      Quality assurance in obstetric and gynecological ultrasound in Hungary.
      ,
      • Szabó I.
      • Csabay L.
      • Tóth Z.
      • Török O.
      • Papp Z.
      Quality assurance in obstetric and gynecologic ultrasound. The Hungarian model.
      This rigorous training program proved to be ahead of its time by decades. Such programs are now commonplace throughout the world. Zoltán also introduced similar training programs in other areas of obstetrics and gynecology at the Women’s Clinic. The present-day nationwide programs are modeled after Zoltán’s pioneering efforts. In Budapest, he organized the Fourth World Congress on Ultrasound in Obstetrics and Gynecology in 1994, and he served for 10 years on the Board of the International Society of Ultrasound in Obstetrics and Gynecology and on the Editorial Board of Ultrasound in Obstetrics & Gynecology.
      In 2018, Zoltán co-organized an international meeting to celebrate the 200th anniversary of the birth of Ignaz Semmelweis. Speakers touched on different aspects of the life and the tragic death of the Hungarian hero. An article authored by Nicholas Kadar and Zoltán Papp emerged from this event. Moreover, it was followed by other articles and books revisiting the extraordinary contribution of Semmelweis, not only to obstetrics but to the philosophy of science
      • Kadar N.
      • Romero R.
      • Papp Z.
      Ignaz Semmelweis: the “Savior of Mothers”: on the 200th anniversary of his birth.
      • Kadar N.
      Rediscovering Ignaz Philipp Semmelweis (1818-1865).
      • Kadar N.
      • Romero R.
      • Papp Z.
      • Kadar N.
      • Kadar N.
      • Croft R.D.
      Why Semmelweis's doctrine was rejected: evidence from the first publication of his results by Friedrich Wieger, and an editorial commenting on the results.
      • Kadar N.
      A note on Semmelweis’s animal experiments and their historical significance.
      • Kadar N.
      Vindicating a traduced genius: Ignaz Philipp Semmelweis (1818-1865).
      (Figure 3).
      Figure thumbnail gr3
      Figure 3Book cover of Semmelweis 200 Éve
      The book, published on the occasion of the 200th anniversary of the birth of Ignaz Semmelweis, introduces the history of the Semmelweis family in the 18th century until the present day. The text presents the main events of a special life and his discovery, with useful consequences. László Rosivall edited the book, published in 2019 and translated for an English edition.
      Romero. Giants in Obstetrics and Gynecology Series: a profile of Zoltán Papp, MD, PhD, DSc, FACOG (Hon). Am J Obstet Gynecol 2022.

      A gynecologic and obstetrical surgeon

      Because of his in-depth knowledge of anatomy and his dexterity, skill, and stamina, Zoltán became the person to call when there were surgical challenges in Budapest. He modified the technique of nerve-sparing radical hysterectomies for stage IB–IIB cervical cancer and performed the procedure more than 1000 times.
      • Papp Z.
      • Csapó Z.
      • Hupuczi P.
      • Mayer Á.
      Nerve-sparing radical hysterectomy for stage IA2-IIB cervical cancer: 5-year survival of 501 consecutive cases.
      An innovator, he developed a technique for transabdominal metroplasties for the treatment of subseptate uteruses, a unique procedure before the hysteroscopic era. This procedure is still useful today in cases of an unsuccessful hysteroscopic resection of the uterine septa and to treat bicornuate uteruses.
      • Papp Z.
      • Mezei G.
      • Gávai M.
      • Hupuczi P.
      • Urbancsek J.
      Reproductive performance after transabdominal metroplasty: a review of 157 consecutive cases.
      He also modified a technique for vaginal vault prolapse after hysterectomy, which consists of a transabdominal partial vaginal resection and an infundibulopelvic colpopexy.
      • Papp Z.
      Infundibulopelvic colpopexy with partial resection of vagina for repair of posthysterectomy vault prolapse.
      ,
      • Papp Z.
      Transabdominal partial vaginal resection and infundibulopelvic colpopexy for posthysterectomy vaginal vault prolapse.
      Furthermore, he has been a long-standing advocate of treating fibroids with myomectomies rather than hysterectomies.
      • Joó J.G.
      • Inovay J.
      • Silhavy M.
      • Papp Z.
      Successful enucleation of a necrotizing fibroid causing oligohydramnios and fetal postural deformity in the 25th week of gestation. A case report.
      • Gávai M.
      • Berkes E.
      • Papp Z.
      Surgery for large uterine fibroids: size is rarely an issue.
      • Gávai M.
      • Berkes E.
      • Fekete T.
      • Lázár L.
      • Takács Z.F.
      • Papp Z.
      Analysis of perioperative morbidity according to whether the uterine cavity is opened or remains closed during abdominal myomectomy--results of 423 abdominal myomectomy cases.
      Zoltán is known for the performance of bilateral hypogastric artery ligations for the treatment of uncontrolled postpartum hemorrhage, which has saved hundreds of uteri and lives.
      • Papp Z.
      Massive obstetric hemorrhage.
      • Papp Z.
      • Tóth-Pál E.
      • Papp C.
      • et al.
      Hypogastric artery ligation for intractable pelvic hemorrhage.
      • Papp Z.
      • Sziller I.
      • Hupuczi P.
      Controlling of profuse pelvic haemorrhage in obstetrics and gynaecology by hypogastric artery ligation.
      According to Dr Nándor Gábor Than, Zoltán’s demeanor in the operating room is confident, calm, decisive, and quick, earning him respect, admiration, and trust. After training generations of gynecologic surgeons in Hungary, Zoltán stepped aside from surgical activities in February of this year at the age of 80.

      Editor-in-Chief of the Orvosi Hetilap

      Launched in 1857, the Orvosi Hetilap, which translates to the Hungarian Medical Weekly, is the sixth oldest medical journal, founded to communicate in Hungarian instead of Latin or German, as was the tradition of that era. Throughout its 165 years of existence, the journal has not only informed the Hungarian medical community, but it has also served as a venue to maintain the Hungarian medical language. As a multispecialty journal, it has been published every Sunday, except for two years during World War II. In 2016, the Hungarian Medical Society appointed Zoltán to the position of Editor-in-Chief at the age of 74 after concluding that Zoltán would be the right leader for the modern times. The Orvosi Hetilap publishes five articles per week, which are personally edited by Zoltán (Figure 4). He has increased the visibility of the journal (print and online) and its impact factor. Indeed, the journal’s website receives more than 500,000 hits per year, and it is the main journal for the Hungarian medical community worldwide. During the COVID-19 pandemic, the journal published nearly 100 papers reporting important observations about SARS-CoV-2 and the disease in Hungary.
      Figure thumbnail gr4
      Figure 4Professor Papp in his home office, 2021, Budapest
      Professor Zoltán Papp, situated in his preferred place of work, writes books and edits the Orvosi Hetilap, the oldest medical scientific publication in Hungary. Photo courtesy of Professor Zoltán Papp.
      Romero. Giants in Obstetrics and Gynecology Series: a profile of Zoltán Papp, MD, PhD, DSc, FACOG (Hon). Am J Obstet Gynecol 2022.

      Leadership in obstetrics and gynecology

      Zoltán’s contribution to the field of obstetrics and gynecology in Hungary is staggering by any standard: the hundreds of publications (in Hungarian and in English), the meetings he has organized, the international awards and honorary degrees he has received, the professional organizations he has chaired or served as a board member, and his editorial activities for many professional journals do not do sufficient justice to what he has been able to achieve during his long career. Of his numerous awards and honors, his acceptance of the Liley Medal and the Roberto Caldeyro-Barcia Lifetime Achievement Award, and his membership on the International Advisory Board of the American Journal of Obstetrics and Gynecology, may be singled out—yet a better indicator of his influence may be his Hirsch index of 46 and the number of citations of his scientific work, exceeding 13,000. He has been a Visiting Professor at Cornell University and at the University of Medicine and Dentistry of New Jersey.

      Zoltán Papp, teacher, mentor, and role model

      Given the publication of more than 40 books, it is difficult to describe the profound impact that Zoltán has had in teaching our discipline and medical genetics in Hungary and beyond. The standard reference of obstetrics and gynecology in Hungary is the Textbook of Obstetrics and Gynecology, originally published in 1999 and now in its sixth edition. As the official textbook for medical students, residents, and fellows, it serves to generate the standards of care in Hungary. From 2016 to 2017, Zoltán published what is now called “The Trilogy:” three books for advanced practitioners of pregnancy care, perinatal medicine, and gynecology
      Papp Z, ed. Textbook of pregnancy care (in Hungarian). Budapest, Medicina Publisher; 2016.
      Papp Z, ed. Textbook of perinatology (in Hungarian). Budapest, Medicina Publisher; 2016.
      Papp Z, ed. Textbook of gynecology (in Hungarian). Budapest, Medicina Publisher; 2017.
      (Figure 5). Other major texts include a book on medical genetics
      (Figure 6), obstetrical genetics
      • Papp Z.
      Obstetric Genetics (with the cooperation of Lindenbaum RH).
      (Figure 7), and two atlases covering diagnostic ultrasound
      (Figure 8) and fetal diagnosis
      • Papp Z.
      • Csécsei K.
      • Lindenbaum R.H.
      • Szeifert G.T.
      • Tóth Z.
      • Váradi V.
      Atlas of fetal diagnosis.
      (Figure 9).
      Figure thumbnail gr5
      Figure 5The “Trilogy,” 2016
      The “Trilogy” is a set of three handbooks written for advanced practitioners of pregnancy care, perinatal medicine, and gynecology, edited by Professor Zoltán Papp. Photo courtesy of Professor Zoltán Papp.
      Romero. Giants in Obstetrics and Gynecology Series: a profile of Zoltán Papp, MD, PhD, DSc, FACOG (Hon). Am J Obstet Gynecol 2022.
      Figure thumbnail gr6
      Figure 6The proceedings of the Symposium on Medical Genetics, Debrecen-Hajdúszoboszló, Hungary, 1976
      The symposium was organized by the University of Debrecen Medical School for medical geneticists who worked behind the Iron Curtain. Sponsored by the World Health Organization, it encouraged the participation of famous experts in human genetics from Western countries. This volume contains the 109 papers presented as conventional and poster lectures during the event. At the invitation of Professor Gábor Szabó, the head of the University’s Department of Medical Biology, Zoltán Papp served as the organizer of the meeting. Together, they edited the publication titled Medical Genetics (Excerpta Medica, Amsterdam–Oxford, 1977).Photo courtesy of Professor Zoltán Papp.
      Romero. Giants in Obstetrics and Gynecology Series: a profile of Zoltán Papp, MD, PhD, DSc, FACOG (Hon). Am J Obstet Gynecol 2022.
      Figure thumbnail gr7
      Figure 7The union of two disciplines: obstetrics and genetics
      Professor Papp’s monograph Obstetric Genetics, first published in Hungarian in 1986, contained basic elements of medical genetics, prenatal genetic counseling, and prenatal screenings, thus uniting the disciplines of obstetrics and genetics. The book was published with the cooperation of Richard H. Lindenbaum (University Department of Medical Genetics, Oxford), and the foreword was written by John M. Opitz, then Editor-in-Chief of the American Journal of Medical Genetics. In 1990, a translation was published by the Hungarian Academic Press in Budapest.Photo courtesy of Professor Zoltán Papp.
      Romero. Giants in Obstetrics and Gynecology Series: a profile of Zoltán Papp, MD, PhD, DSc, FACOG (Hon). Am J Obstet Gynecol 2022.
      Figure thumbnail gr8
      Figure 8An atlas of contributions to ultrasound diagnosis by Hungarian scientists, 2019
      The Atlas of Ultrasound in Obstetrics and Gynecology is a selected collection of more than 2500 ultrasound images and over 500 color illustrations. The work of 13 Hungarian obstetricians, mostly students of Professor Papp, depicted the last 40 years of progress in the field of ultrasound diagnosis in obstetrics and gynecology. The volume, coedited by Professor Papp, underscores the significant contributions of Hungarian obstetricians and gynecologists that have revolutionized the field. The volume was published in Hungarian by Golden Book Publishers, Budapest.Photo courtesy of Professor Zoltán Papp.
      Romero. Giants in Obstetrics and Gynecology Series: a profile of Zoltán Papp, MD, PhD, DSc, FACOG (Hon). Am J Obstet Gynecol 2022.
      Figure thumbnail gr9
      Figure 9Fetal diagnoses in illustration, 1992
      The Atlas of Fetal Diagnosis is a selected collection of 400 color fetopathologic photographs of several forms of fetal malformations, disruptions, deformations, and chromosome aberrations. The volume, illustrated by 100 ultrasound images, shows those diagnosed prenatally between 1977 and 1989 at the University Department of Obstetrics and Gynecology in Debrecen, Hungary. The book was published with the cooperation of five contributors and the students of the author; the foreword was written by John M. Opitz, Editor-in-Chief of the American Journal of Medical Genetics.With permission.
      Romero. Giants in Obstetrics and Gynecology Series: a profile of Zoltán Papp, MD, PhD, DSc, FACOG (Hon). Am J Obstet Gynecol 2022.
      In addition to the scientific papers, congresses, and symposia, the physicians and scientists who trained with him in Debrecen and Budapest are living testimony of Zoltán’s seminal contributions to obstetrics and gynecology, medicine, and science. He has served as a thesis mentor for over 50 PhD dissertations. His mentees are now in positions of leadership in departments, hospitals, and research institutions worldwide.
      To recognize Zoltán’s contributions for his 80th birthday, organized by his successor Dr Petronella Hupuczi, Semmelweis University bestowed its highest honor, the Pro Universitate Award, and commissioned a portrait that now appears with the portraits of Semmelweis and his successors (Figure 10).
      Figure thumbnail gr10
      Figure 10Portrait of Zoltán Papp at Semmelweis University, 2022
      For his 80th birthday, Semmelweis University honored Professor Papp with the Pro Universitate Award and commissioned a portrait that appears with the portraits of Ignaz Semmelweis and his successors at the Women’s Clinic. In the portrait painted by Dr Anikó Boda, Professor Papp’s hand rests on Obstetrics and Gynecology, the official textbook for medical students, residents, and fellows in Hungary since 1999; it is now in its sixth edition.Photo courtesy of Professor Zoltán Papp.
      Romero. Giants in Obstetrics and Gynecology Series: a profile of Zoltán Papp, MD, PhD, DSc, FACOG (Hon). Am J Obstet Gynecol 2022.

      Personal life and words to live by

      Zoltán took an early interest in music and started to like opera from the age of 10. He played the clarinet and saxophone in jazz bands in high school and at university, but his enthusiasm for jazz and opera never left him, and he still frequently listens to his favorites: Tim Laughlin, the New Orleans jazz clarinetist; Joe Murányi, the late saxophonist whose parents emigrated to the United States from Zoltán’s native village; Vicenzo Bellini’s “Norma” and “The Puritans;” and Giuseppe Verdi’s “La Traviata” and “Rigoletto.” Zoltán also frequently listens to classical music, particularly the works of Mozart, Beethoven, Liszt, and Chopin. “I can really immerse myself in a beautiful piece of music,” he said.
      Zoltán is also a nature and animal lover— he has enjoyed the company of three dogs. His house sits along the perimeter of a forest close to his favorite walking paths, and his garden is full of plants and flowers.
      Zoltán and Valéria have two children: a son, Zoltán, who holds a PhD in aerospace sovereignty and is an expert in international law, and a daughter, Eszter, who is an attorney. One of the great joys of Zoltán’s life are his five grandchildren. Recently, he published his autobiography,
      • Papp Z.
      A szatmári Nagy-Károlytól Budapestig – önéletrajzi zárójelentés (in Hungarian).
      dedicated to his family. In the opening pages, Zoltán said that he has lived by the words of the Hungarian poet, Dezső Keresztury, which aptly sum up his philosophy: “I am not better than others, I just do my job.”

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        Cytogenetic analysis of cord-blood lymphocytes.
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        Prenatal diagnosis and pathoanatomy of iniencephaly.
        Clin Genet. 1986; 30: 81-86
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        Incidence and associations of single umbilical artery in prenatally diagnosed malformed, midtrimester fetuses: a review of 62 cases.
        Am J Med Genet. 1992; 43: 524-530
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        Prenatal diagnosis and management of chondrodysplasias.
        Acta Chir Hung. 1989; 30: 281-289
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        Congenital diaphragmatic hernia: can prenatal ultrasonography predict outcome?.
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        Ann N Y Acad Sci. 1998; 847: 21-45
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        Post-termination dysmorphological studies and genetic counseling.
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        Computer follow-up system for obstetric, genetic and neonatal care in Hungary.
        Int J Gynaecol Obstet. 1993; 43: 323-324
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        Quality and quantity ratios of obstetric care in the gypsy and non-gypsy population in Hungary.
        Int J Gynaecol Obstet. 1994; 46: 63-64
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        Impact of prenatal mid-trimester screening on the prevalence of fetal structural anomalies: a prospective epidemiological study.
        Ultrasound Obstet Gynecol. 1995; 6: 320-326
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        Maternal age-dependent and sex-related changes of gestational serum alpha-fetoprotein.
        Fetal Diagn Ther. 1995; 10: 368-372
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        First trimester chorionic villus sampling for DNA analysis.
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        Ethical issues in genetic counseling.
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        Molecular analysis of cystic fibrosis in the Hungarian population.
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        The occurrence of various non-delta F508 CFTR gene mutations among Hungarian cystic fibrosis patients.
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        Rapid prenatal detection of aneuploidies by fluorescent polymerase chain reaction.
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        Prenat Diagn. 1998; 18: 669-674
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        Same day diagnosis of Down’s syndrome and sex in single cells using multiplex fluorescent PCR.
        Mol Pathol. 1998; 51: 164-167
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        Rapid determination of trisomy 18 parental origin using fluorescent PCR and small tandem repeat markers: case reports.
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        Rapid trisomy diagnosis (21, 18, and 13) using fluorescent PCR and short tandem repeats: applications for prenatal diagnosis and preimplantation genetic diagnosis.
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        Presymptomatic diagnosis of familial colon polyposis.
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        Detection of CAG repeats using silver staining in patients with Huntington disease in Hungary.
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        Questions and problems in direct predictive testing for Huntington’s disease.
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        PCR reagents for detection of (CAG)n repeats in Huntington disease.
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        Detection of mtDNA deletion in Pearson syndrome by two independent PCR assays from Guthrie card.
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        • Papp Z.
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        Nerve-sparing radical hysterectomy for stage IA2-IIB cervical cancer: 5-year survival of 501 consecutive cases.
        Eur J Gynaecol Oncol. 2006; 27: 553-560
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