Hepatitis B-related hepatocellular carcinoma in a 36-year-old pregnant woman: prognosis and management dilemma.

Management of chronic hepatitis B infection complicated by hepatocellular carcinoma (HCC) in pregnancy poses a treatment dilemma as the pregnancy accelerates disease progression and narrows the diagnostic tools and therapeutic choices. Studies have reported higher maternal and fetal losses. We share our experience with a 36-year-old pregnant woman who presented at 35 weeks' gestation with a large painful nodular liver and significant weight loss. She tested HBsAg-positive and had both clinical and laboratory features of severe liver decompensation. The abdominal ultrasound rightly described HCC on a cirrhotic background. The fetus was delivered by cesarean section but the mother died soon after.

Clinical outcome of high-grade cervical intraepithelial neoplasia during pregnancy: A 10-year experience.

OBJECTIVE: To investigate the clinical outcome of high-grade cervical intraepithelial neoplasia (CIN) diagnosed by colposcopy-directed biopsy during pregnancy and to evaluate the risk factors for persistent disease. STUDY DESIGN: This retrospective study included pregnant women who were diagnosed with CIN2+ by colposcopy-directed biopsy from January 2005 to December 2014. The clinical characteristics, histopathologic results, and human papillomavirus (HPV) test results were reviewed. The final histopathologic result after delivery was compared with the initial diagnosis to determine disease progression, persistence, or regression. RESULTS: During the 10-year period, 215 pregnant women were diagnosed with high-grade CIN (75 CIN2, 140 CIN3) by colposcopy-directed biopsy. The mean age of the patients was 30.4 years. A total of 187 patients (87.0%) had high-risk HPV infections, with 76 (35.3%) infections identified as HPV genotype 16 or 18. Excisional procedures for diagnosis and treatment were not performed during pregnancy. The histopathologic results of 160 patients (normal in 43, CIN1 in 10, CIN2 in 15, CIN3 in 89, and invasive cancer in 3) were evaluated during the postpartum period. Multivariate logistic regression analysis was performed, and postpartum high-risk HPV infection (OR 5.09; 95% CI 2.15-12.05; P < 0.001) was identified as a significant independent predictor of CIN2+ persistence. CONCLUSIONS: Conservative management of CIN2-3 during pregnancy is acceptable. However, persistent high-risk HPV infection is a major risk factor for CIN2+ persistence. Close follow-up with HPV testing, and postpartum colposcopy evaluation are necessary.

Colpocytological abnormalities in HIV infected and uninfected pregnant women: prevalence, persistence and progression.

In this retrospective case-control study, we analyse data of 48 HIV-positive pregnant patients, versus a control group of 99 HIV-negative pregnant women, followed as outpatients by our department from 2009 to 2014. The aims of the study were to investigate the prevalence, persistence and progression of cervical squamous intraepithelial lesions (SIL) in each group and to correlate colpo-cytological lesions to the socio-demographic and clinical-laboratory findings in the HIV + pregnant women. In our study we observed that immunosuppression, HPV infection and vaginal coinfections were predictive of cervical lesions. Pap smear and colposcopy should be part of routine care for HIV-infected pregnant women because these lesions behave aggressively in these patients. Success of prevention depends on massive access of patients to screening. HAART reduces viral load and maintains CD4 count and can affect progression of SIL. Multidisciplinary services on the same site appear to be one promising strategy to improve compliance in patients. Impact Statement What is already known on this subject: Our study provided novel information on a highly vulnerable population of young HIV + pregnant women. What the results of this study add: We observed that immunosuppression, HPV infection and vaginal coinfections were predictive of cervical lesions remarkable with colposcopy. We could consider these important risk factors to evaluate to establish an appropriate strategy of management for these patients. What the implications are of these findings for clinical practice and/or further research: Association of the risk between SIL presence and HIV and HPV infection also deserves additional investigation. We believe that Pap smears and colposcopies should be part of the routine care for HIV-infected women because these lesions behave particularly aggressively in these patients.

Neutralizing and IgG antibodies against simian virus 40 in healthy pregnant women in Italy.

OBJECTIVE: Polyomavirus simian virus 40 (SV40) sequences have been detected in various human specimens and SV40 antibodies have been found in human sera from both healthy individuals and cancer patients. This study analyzed serum samples from healthy pregnant women as well as cord blood samples to determine the prevalence of SV40 antibodies in pregnancy. METHODS: Serum samples were collected at the time of delivery from two groups of pregnant women as well as cord bloods from one group. The women were born between 1967 and 1993. Samples were assayed by two different serological methods, one group by neutralization of viral infectivity and the other by indirect ELISA employing specific SV40 mimotopes as antigens. Viral DNA assays by real-time polymerase chain reaction were carried out on blood samples. RESULTS: Neutralization and ELISA tests indicated that the pregnant women were SV40 antibody-positive with overall prevalences of 10.6% (13/123) and 12.7% (14/110), respectively. SV40 neutralizing antibodies were detected in a low number of cord blood samples. Antibody titers were generally low. No viral DNA was detected in either maternal or cord bloods. CONCLUSIONS: SV40-specific serum antibodies were detected in pregnant women at the time of delivery and in cord bloods. There was no evidence of transplacental transmission of SV40. These data indicate that SV40 is circulating at a low prevalence in the northern Italian population long after the use of contaminated vaccines.

High-risk human papilloma virus management in pregnancy with cervical intraepithelial neoplasia during pregnancy and postpartum in China.

AIM: To investigate the relationship between cervical intraepithelial neoplasia (CIN) and high-risk human papilloma virus (HR-HPV) during pregnancy and postpartum in China. METHODS: In this prospective case-control study, 168 pregnant women with CIN and cervicitis were diagnosed by colposcopic cervical biopsy. All the cases underwent hybrid capture assay version II (HCII) to detect HR-HPV DNA load amounts and the tests were completed in 3-6 months after childbirth. RESULTS: During pregnancy: as the CIN grade increased, the HR-HPV infection rates increased (P = 0.002), but HR-HPV DNA load amounts (in logarithms) did not change obviously (P = 0.719). 3-6 months postpartum: as the CIN grade increased, the natural negative rate of HR-HPV decreased (P = 0.000), while the amount of HR-HPV DNA (in logarithms) increased (P = 0.036); especially the amount of HR-HPV DNA in pregnant women with CINIII was significantly higher than that of other grades. During pregnancy and 3-6 months postpartum : the amount of HR-HPV DNA (in logarithms) during pregnancy was higher than that of 3-6 months postpartum with the same grade of CIN. CONCLUSION: The findings emphasize the importance of undergoing the HCII test 3-6 months postpartum. It should be noted that HR-HPV may turn negative in pregnancy with CINIII 3-6 months after childbirth. Further treatments of pregnancy with CIN should be considered according to the CIN grade diagnosed by cervical biopsy via colposcopy 3-6 months after birth, but not according to the persistence of HR-HPV during pregnancy.

Kaposi's sarcoma and pregnancy: case report and literature review.

We report the observation of cutaneous Kaposi's sarcoma (KS) worsening during the second trimester of pregnancy in 2 African women. Both patients were tested seronegative for HIV. They had no complication during their pregnancy, and no evidence of extracutaneous disease was found, allowing therapeutic abstention. They gave birth to healthy children showing no clinical evidence of human herpesvirus 8 (HHV-8) infection. Based on these observations and on the review of the literature, we discuss the risk of vertical transmission of HHV-8 as well as the impact of pregnancy on KS.

Head and neck squamous cell carcinoma in pregnant women.

BACKGROUND: The aim of this study was to investigate oral cancer in pregnant women, a rare but therapeutically challenging patient subset. METHODS: After institutional review board approval, an EMERSE search was used to identify all women treated at the University of Michigan from 1998 to 2010 with head and neck squamous cell carcinoma (HNSCC) during pregnancy. This identified 4 patients with tongue cancer. Biomarkers and human papillomavirus (HPV) were assessed by immunohistochemistry and multiplex PCR/mass spectrometry, respectively. RESULTS: Two patients responded well to therapy and are alive more than 10 years after diagnosis; 2 patients died of disease. All tumors overexpressed EGFR and Bcl-xL, 3 of 4 overexpressed c-Met, both tumors that progressed overexpressed p53. All tumors were negative for HPV, p16, estrogen receptor, progesterone receptor, and HER-2. CONCLUSIONS: Biomarkers of aggressive tumors (high EGFR, c-Met; high Bcl-xL-low p53) did not correlate with outcome. Additional studies are needed to determine whether perineural invasion, delay in diagnosis, and p53 overexpression are factors in poor survival.

Productive infection of bovine papillomavirus type 2 in the placenta of pregnant cows affected with urinary bladder tumors.

Papillomaviruses (PVs) are believed to be highly epitheliotropic as they usually establish productive infections within stratified epithelia. In vitro, various PVs appear to complete their entire life-cycle in different trophoblastic cell lines. In this study, infection by and protein expression of bovine papillomavirus type 2 (BPV-2) in the uterine and chorionic epithelium of the placenta has been described in four cows suffering from naturally occurring papillomavirus-associated urothelial bladder tumors. E5 oncoprotein was detected both by Western blot analysis and immunohistochemically. It appears to be complexed and perfectly co-localized with the activated platelet-derived growth factor ß receptor (PDGFßR) by laser scanning confocal microscopy. The activated PDGFßR might be involved in organogenesis and neo-angiogenesis rather than in cell transformation during pregnancy. The major capsid protein, L1, believed to be only expressed in productive papillomavirus infection has been detected by Western blot analysis. Immunohistochemical investigations confirmed the presence of L1 protein both in the cytoplasm and nuclei of cells of the uterine and chorionic epithelium. Trophoblastic cells appear to be the major target for L1 protein expression. Finally, the early protein E2, required for viral DNA replication and known to be expressed during a productive infection, has been detected by Western blot and immunohistochemically. Electron microscopic investigations detected viral particles in nuclei of uterine and chorionic epithelium. This study shows that both active and productive infections by BPV-2 in the placenta of pregnant cows can occur in vivo.

Ovarian squamous cell carcinoma which metastasized 8 years after cervical conization for early microinvasive cervical cancer: a case report.

Squamous cell cervical carcinoma that metastasized to the ovary is common in patients with bulky tumors or locally advanced disease; however, ovarian squamous cell carcinoma that metastasized after cervical conization surgery for early microinvasive uterine cervical carcinoma is very rare. We present a case of ovarian squamous cell carcinoma that metastasized 8 years after cervical conization surgery for early microinvasive cervical carcinoma. She had no sign of recurrence in the uterine cervix. We detected human papillomavirus type 16 DNA in both cervical tissue and ovarian tissue, suggesting that ovarian squamous cell carcinoma is derived from microinvasive cervical cancer. Although there are very few cases of early microinvasive squamous cell carcinoma that metastasized to the ovary with delayed recurrence, we should pay attention strictly not only to the cervical condition but also to the ovarian condition on regular post-operative follow-up.

Association between Epstein-Barr virus infection and risk for development of pregnancy-associated breast cancer: joint effect with vitamin D?

BACKGROUND: Few studies have evaluated the role of the ubiquitous Epstein-Barr virus (EBV) infection, together with levels of the immunomodulator, vitamin D, in different breast cancer entities. We studied, prospectively, the association of EBV and vitamin D status with the risk of pregnancy-associated breast cancer (PABC), breast cancer diagnosed during pregnancy or 1 year post-partum, using a nested case-control study. METHODS: Serum vitamin D and antibodies to EBV were measured for 108 PABC cases of the Finnish Maternity Cohort, and 208 controls matched for date of birth, date of sampling and parity. The joint effect of vitamin D and EBV on the risk of PABC was evaluated. RESULTS: EBV seropositivity was generally not associated with the risk of PABC. Among individuals with sufficient (≥75 nmol/l) levels of vitamin D, we, however, found similar increased risk estimates for PABC associated with serum immunoglobulin G (IgG) antibodies to EBV early antigens [odds ratio (OR)=7.7, 95% (confidence interval) CI 1.4-42.3] and the viral reactivator protein, ZEBRA (OR=7.8, 95% CI 1.1-61.2). CONCLUSION: Immunological markers of EBV reactivation status among individuals with sufficient vitamin D levels were consistently associated with increased risk of the disease. This suggests that EBV reactivation may be an indicator of the progression of breast cancer occurring soon after pregnancy, while the virus probably is not the aetiological agent.

Endocervical adenocarcinoma in situ with ovarian metastases: a unique variant with potential for long-term survival.

Adenocarcinoma in situ (AIS) of the endocervix is typically confined to the cervix, but may be extensive. We report 2 cases of extensive AIS-one with intraendometrial spread-that recurred after cone biopsy and were associated with ovarian metastases. In both cases, primary and metastatic tumors were positive for human papillomavirus 16. Both patients are currently disease-free and one has had no recurrence after a follow-up period of 145 months. Extensive, recurring AIS is a rare variant that may be unique for its risk of coincident ovarian involvement. However, ovarian spread, albeit rare, does not invariably result in an adverse outcome.

Burkitt's lymphoma related to Epstein-Barr virus infection during pregnancy.

SETTING: Burkitt's lymphoma is a rare form of cancer and is an extremely rare diagnosis during pregnancy. This form of lymphoma is a very fast growing B cell neoplasm and chemotherapy is the treatment of choice for the disease in all its stages. CASE REPORT: The authors describe the case of a Caucasian 40-year-old nulliparous woman, with previous known Epstein-Barr virus infection, that presents at 28 weeks gestation with supraclavicular adenopathy and multiple bilateral breast nodules, in which biopsy showed non-Hodgkin lymphoma, Burkitt's type. DISCUSSION: There are few described cases of Burkitt's lymphoma during pregnancy and in general the outcomes have been poor. In most of the cases, the patients were not treated by current standards or instead had a late diagnosis. This neoplasia is the most rapidly progressive human tumor, and any delay in initiating therapy can adversely affect patient's prognosis. The authors discuss treatment options in pregnancy and its perinatal implications.

Detection of integrated human papillomavirus by human papillomavirus types 16 and 18 in situ hybridization: a valuable diagnostic tool in diagnosing cervical carcinoma?

Human papillomavirus (HPV) infection is an important factor in cervical carcinogenesis. We describe 3 cases of patients with difficulties in diagnosing either a primary or recurrent cervical carcinoma. These cases illustrate that detection of integrated HPV is helpful in diagnosing cervical carcinoma.

ACOG Practice Bulletin No. 99: management of abnormal cervical cytology and histology.

Recent evidence has shown that the risk of malignant and premalignant cervical disease and human papillomavirus (HPV) infections varies significantly with age (1,2). Furthermore, evidence now shows that treatment for cervical disease carries significant risk for future pregnancies (3-7). These factors have led to a re-evaluation of the guidelines for the management of premalignant cervical disease. The purpose of this document is to define strategies for diagnosis and management of abnormal cervical cytology and histology results. In this document, HPV refers to high-risk oncogenic forms of the virus.

Condiloma acuminado e gestação: transmissão vertical e tratamento / Condyloma acuminata and pregnancy: perinatal transmission and treatment

Atualmente, a infecção genital pelo Papilomavírus Humano (HPV) é a doença sexualmente transmissível mais comum entre adultos jovens sexualmente ativos. Estima-se que aproximadamente 10 a 60% das mulheres com vida sexual ativa estejam infectadas pelo HPV. As verrugas anogenitais decorrentes da infecção pelo HPV denominadas condilomas acuminados são a forma clínica mais comum da doença. Na gestação, o condiloma acuminado é a manifestação mais comum da infecção pelo HPV, com incidência variando de 11,6 a 51,7%. Sabe-se que durante o período gravídico ocorrem mudanças fisiológicas na genitália feminina que, somadas a alterações imunológicas inerentes à gestação, criam ambiente propício à proliferação do HPV. Além disso, os modos de transmissão vertical e as conseqüências para o produto conceptual têm sido amplamente estudados. Durante a gestação, são de fundamental importância os tratamentos eficazes, visando a baixas taxas de recorrência materna e mínimos efeitos deletérios para o feto.

Nowadays, the Human Papilomavirus (HPV) infection of the lower genital tract is the most common sexually transmitted disease among young people who are sexually active. It is said that approximately 10% a 60% of women that have a sexual contact are contaminated with HPV. The genital warts from the HPV infection denominated condyloma acuminata are the most common clinical form of the disease in pregnancy, the condyloma acuminata is the most common manifestation of the infection of HPV with and incidence that ranges from 11,6% to 51,7%. It is of knowledge that during the gestation period physiologic changes of the female genitalia occur, and this fact added to immunology alterations expected at pregnancy, made the local environment optimal for the viral proliferation. Moreover, the modes of vertical transmission and the fetal consequences are being extensively studied. During pregnancy, it is of fundamental importance an efficient treatment, which provides lower rates of recurrences and without deleterious effects for the concept.

Viral regulation of aquaporin 4, connexin 43, microcephalin and nucleolin.

The current study investigated whether human influenza viral infection in midpregnancy leads to alterations in proteins involved in brain development. Human influenza viral infection was administered to E9 pregnant Balb/c mice. Brains of control and virally-exposed littermates were subjected to microarray analysis, SDS-PAGE and western blotting at three postnatal stages. Microarray analysis of virally-exposed mouse brains showed significant, two-fold change in expression of multiple genes in both neocortex and cerebellum when compared to sham-infected controls. Levels of mRNA and protein levels of four selected genes were examined in brains of exposed mice. Nucleolin mRNA was significantly decreased in day 0 and day 35 neocortex and significantly increased in day 35 cerebellum. Protein levels were significantly upregulated at days 35 and 56 in neocortex and at day 56 in cerebellum. Connexin 43 protein levels were significantly decreased at day 56 in neocortex. Aquaporin 4 mRNA was significantly decreased in day 0 neocortex. Aquaporin 4 protein levels decreased in neocortex significantly at day 35. Finally, microcephalin mRNA was significantly decreased in day 56 neocortex and protein levels were significantly decreased at 56 cerebellum. These data suggest that influenza viral infection in midpregnancy in mice leads to long-term changes in brain markers for enhanced ribosome genesis (nucleolin), increased production of immature neurons (microcephalin), and abnormal glial-neuronal communication and neuron migration (connexin 43 and aquaporin 4).