Ioannis N. Mammas

Human papilloma virus (HPV) infection in children and adolescents

Human papilloma viruses (HPV) are common pathogens associated with a wide range of cutaneous and mucosal infections in childhood. Different HPV types can cause common warts, genital warts, low-grade as well as high-grade squamous intraepithelial lesions. Anogenital warts represent an issue with legal and clinical implications and evaluation of children for the possibility of sexual abuse should be considered in all cases. Recurrent respiratory papillomatosis has also been associated with HPV infection in a variety of studies. The recently introduced HPV vaccination is expected to prevent HPV-related cervical cancer in adulthood; however, HPV infection will continue to affect children.

Molecular detection methods of human papillomavirus (HPV)

Human papillomavirus (HPV) testing can identify women at risk of cervical cancer. Currently, molecular detection methods are the gold standard for identification of HPV. The three categories of molecular assays that are available are based on the detection of HPV DNA and include (1) non-amplified hybridization assays, such as Southern transfer hybridization (STH), dot blot hybridization (DB) and in situ hybridization (ISH); (2) signal amplified hybridization assays, such as hybrid capture assays (HC2); (3) target amplification assays, such as polymerase chain reaction (PCR) and in situ PCR. STH requires large amounts of DNA, is laborious and not reproducible, while ISH has only moderate sensitivity for HPV. The sensitivity of the HC2 assay is similar to that of PCR-based assays, with high sensitivity being achieved by signal rather than target amplification. PCR-based detection is both highly sensitive and specific. Since PCR can be performed on very small amounts of DNA, it is ideal for use on specimens with low DNA content. In the future, with the advance of technology, viral DNA extraction and amplification systems will become more rapid, more sensitive, and more automated.

Human papilloma virus (HPV) and host cellular interactions.

Viral-induced carcinogenesis has been attributed to the ability of viral oncoproteins to target and interact with the host cellular proteins. It is generally accepted that Human papilloma virus (HPV) E6 and E7 function as the dominant oncoproteins of ‘high-risk’ HPVs by altering the function of critical cellular proteins. Initially it was shown that HPV E6 enhances the degradation of p53, while HPV E7 inactivates the function of the retinoblastoma tumor suppressor protein Rb. However, recent studies during the last decade have identified a number of additional host cellular targets of both HPV E6 and E7 that may also play an important role in malignant cellular transformation. In this review we present the interactions of HPV E6 and E7 with the host cellular target proteins. We also present the role of DNA integration in the malignant transformation of the epithelial cell.

Vaccination against Human Papilloma Virus (HPV): Epidemiological Evidence of HPV in Non-genital Cancers

Recently, the vaccine against human papillomavirus (HPV) was introduced in the national vaccination programmes of several countries worldwide. The established association between HPV and the progression of cervical neoplasia provides evidence of the expected protection of the vaccine against cervical cancer. During the last two decades several studies have also examined the possible involvement of HPV in non-genital cancers and have proposed the presence of HPV in oesophageal, laryngeal, oropharyngeal, lung, urothelial, breast and colon cancers. The possible involvement of HPV in these types of cancer would necessitate the introduction of the vaccine in both boys and girls. However, the role of HPV in the pathogenesis of these types of cancer has yet to be proven. Moreover, the controversial evidence of the possible impact of the vaccination against HPV in the prevention of non-genital cancers needs to be further evaluated. In this review, we present an overview of the existing epidemiological evidence regarding the detection of HPV in non-genital cancers.

Human Papilloma Virus in Hyperplastic Tonsillar and Adenoid Tissues in Children

Background: Human papillomavirus (HPV) in childhood causes skin and anogenital warts as well as the recurrent respiratory papillomatosis, a life-threatening cause of upper airway obstruction in children. To date, the information on HPV infection in tonsillar and adenoid hyperplasia in children is limited. Purpose: The purpose of this study was to investigate the presence of HPV DNA in children with benign tonsillar and/or adenoid hyperplasia. Methods: One hundred six samples of paraffin-embedded adenoid and/or tonsillar tissues from 102 children, 57 girls and 45 boys (age range, 2–14 years), were tested for the presence of HPV DNA using polymerase chain reaction (PCR) with general primers GP5+/GP6+. HPV typing was performed by PCR with specific primers for HPV-16, -18, -33 and -11. Results: HPV DNA was detected in 9 (8.5%) of the 106 collected specimens. The frequencies of HPV typing were 6 of 9 (66.7%) for HPV-16, 2 of 9 (22.2%) for HPV-11, zero of 9 (0%) for HPV-33 and HPV-18, whereas one HPV-positive sample remained untyped. No multiple HPV infection was detected. HPV was detected in 6 (9.4%) children with tonsillar hyperplasia and in 3 (7.1%) with adenoid hyperplasia. The mean age of children with HPV-positive specimens was lower than that of HPV-negative children (P = 0.006). No statistical correlation in the prevalence of HPV infection was observed according to childrens sex, origin or residence (urban or rural). Conclusion: Although the significance of the presence of HPV DNA in tonsillar and adenoid hyperplasias remains obscure, the PCR detection of high-risk HPV DNA should be evaluated cautiously.

Fruit and vegetables consumption in relation to health and diet of medical students in Crete, Greece.

In Greece, prevalence of cardiovascular disease has been increasing during the last few decades. From a public health point of view, it is important to identify lifestyle practices associated with cardiovascular disease risk factors. As part of the Clinical Nutrition course at the University of Crete School of Medicine, 507 medical students (292 men, 215 women) were examined during the period 1995-2001. Individual 24-hour dietary recalls were taken, lifestyle questionnaires were completed, and anthropometric and serum lipid measurements were performed. Fruits and vegetables were consumed by 90% of men (370 +/- 275 g/day) and 94% of women (354 +/- 283 g/day). Among non/ex-smokers who ate fruit and vegetables, 41% consumed > or = 400 g/day, compared to 31% of current smokers (p = 0.05). The risk for high-density lipoprotein cholesterol (HDL-C) < 35 mg/dL, low-density lipoprotein cholesterol (LDL-C) > 130 mg/dL, and total cholesterol/HDL-C ratio (TC:HDL-C) > or = 5 decreased with increasing quartile of fruit and vegetables consumption (trend p < 0.01). Fruit and vegetable intake was favorably related to intake of dietary fiber, calcium, magnesium, potassium, folate, and vitamins C, E, A, B1 and B6, and inversely related to saturated and trans fatty acids and cholesterol. Prospective studies should be performed within the general young adult population to assess the long-term effects of fruit and vegetable consumption on chronic disease risk development.

Nutrient intake and food consumption among medical students in Greece assessed during a Clinical Nutrition course.

The objective of this study was to determine nutrient intake and food consumption patterns among medical students at the University of Crete, Greece. As part of the Clinical Nutrition course from 1989 to 2001, a total of 951 third-year medical students (500 male, 451 female) aged 22±2 years underwent dietary interview, during which individual 24-h dietary recalls were taken. The students also completed a questionnaire on smoking habits, and anthropometric measurements were performed. The Mann–Whitney test was applied to assess differences in nutrient and food group intake between lower and higher fat eaters. Analysis of covariance was used to study relationships between nutrient intakes and tobacco use, adjusting for gender, age, and body mass index. The mean daily energy intake was 2493 kcal (10437 kJ) for males and 1675 kcal (7012 kJ) for females. The contribution of total fat to energy intake was 40% in each gender. Lower fat eaters (≤34.3% of total energy) had higher intakes of fiber (P<0.01), vitamin C (P<0.01) and fruits (P<0.05), and a lower consumption of red meat (P<0.01) than students in the upper fat quartile (≥46.0% of total energy). Smokers had higher intakes of energy (P<0.05) and saturated fatty acids (P<0.01), and lower intakes of fiber (P<0.001), folate (P<0.05) and vitamin C (P<0.001) than non-smokers/ex-smokers. Our results indicate a need for Greek medical students to improve their dietary and health habits. Dietary assessment could be used to enhance nutrition education in medical schools.

The paediatric story of human papillomavirus (Review)

Human papillomavirus (HPV) is composed of a particularly heterogeneous family of DNA viruses, which has gained much attention in recent years due to the discoveries of Professor Harald zur Hausen, who first identified a connection between HPV and cervical cancer. Professor Harald zur Hausen, the ‘Father of HPV Virology’, was the recipient of the 2008 Nobel Prize. HPV can be transmitted through physical contact via autoinoculation or fomites, sexual contact, as well as vertically from the HPV-positive mother to her newborn, causing subclinical or clinical infections. In infancy and childhood, HPV-associated clinical infections include skin warts, genital warts and juvenile recurrent respiratory papillomatosis, while cervical squamous intraepithelial lesions have also been reported among adolescent girls. To date, several research teams, worldwide, have extensively investigated HPV from the paediatric point of view. This primitive effort has been performed before the recent great expansion of paediatric HPV research due to the vaccination programmes against HPV, which were introduced into clinical practice in 2006. In this review article, we present a brief overview of paediatric HPV research after the first report in 1978 involving children in the research of HPV until the time point of this great expansion. In the future, it is expected that further unresolved issues will be addressed and clarified, as the paediatric story of HPV remains a challenging research target.

Novel human papilloma virus (HPV) genotypes in children with recurrent respiratory papillomatosis.

IntroductionRecurrent respiratory papillomatosis (RRP) is characterized by the presence of benign virally induced tumors of the larynx and respiratory epithelium that may obstruct the airway and tend to recur frequently. RRP is caused by the human papilloma virus (HPV), most frequently by HPV types 6 and 11. In this study, we present four cases of children with RRP in whom HPVs other than HPV-6 or HPV-11 were found.Material and methodsIn all four cases, HPV typing was performed by polymerase chain reaction (PCR) followed by restriction digestion (RFLP) in biopsy samples collected during surgery.ResultsIn the first case, simultaneous HPV infection with types 13 and 39 was detected, while in the second case HPV-40 and HPV-56 were found. In cases 3 and 4, the biopsy samples were positive for unidentified ‘low-risk’ HPVs.ConclusionsThe presence of novel HPV genotypes in children with RRP emphasizes the need for further investigation of the implication of these genotypes in the disease.

Water aspiration syndrome at birth – report of two cases

Under-water birth has been considered as a safe method of delivery for healthy women with uncomplicated pregnancies after appropriate selection of women and respect of hygiene rules. However, perinatal morbidity after under-water births is not as rare as it has been considered initially. We present the cases of two neonates, who were transferred to our neonatal unit during the last 12-month period with water aspiration after their uneventful under-water birth.