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人乳头瘤病毒的母婴传播  

2014-04-09 22:32:23|  分类: 专业频道 |  标签: |举报 |字号 订阅

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ANALYSIS  OF  MECHANISMS  FOR  MATERNAL-FETAL TRANSMISSION OF  HUMAN  PAPILLOMAVIRUS

人乳头瘤病毒的母婴传播 - oceanpark - oceanpark的博客
  

 
Abstract
Objective:
To study the relationship between juvenile laryngeal papillomatosis ( JLP ) and genital condyloma acuminata and the mechanism for maternal-fetal transmission of human papillomavirus.
Patients and methods: Samples from 17 cases with JLP were studied by histopathological observation and demonstrating the capsid antigen of human papillomavirus.
Results: The histopathological changes of JLP are analogous to that of genital condyloma. The viral antigens were presented in paraffin sections of these cases.
Conclusions: Maternal-fetal transmission of the etiologic virus occurs mainly during the birth process as newborns pass through the infected birth canal, and it may also occur intrauterine infection via ascending infection or transplacental hematogenous transmission.

  
   As the incidence of condyloma acuminata for adults has shown a steady increase in recent decades, human papillomavirus ( HPV ) infection in children seems to be more common today than in the past. Many pathogens can be trans-mitted from mothers to neonates during perinatal time. It is called maternalfetal transmission, or vertical transmission. That fetus may infect HPV from mothers with genital condyloma during delivery as they pass through the infected birth canal and cause laryngeal papillomas was mentioned in recent years in internal medical journal1 , but few literature on detailed investigation  about it was published. For the sake of learning the possible mechanisms of maternal-fetal transmission of HPV, 17 cases with juvenile laryngeal papillomatosis (JLP ), under 6 years old, were studied by histopathological observation and immunope-roxidase staining for capsid antigen of HPV (HPV-Ag).
 
Materials and Methods
Patients
  All cases were in-patients of our hospital from March, 1988 to May, 1995 except 1case was hospitalized in 1981. The ratio of male and female was 11:6.  The clinical symptoms of the patients were hoarseness, stridor, respiratory distress. Clinical examination showed multiple papules or clusters of multidigi-tated papillary growth with pink-colored and 0.1 to 0.5 cm in size, involved in uvula, epiglottis, palate, glottis, vocal cords, the entry of the esophagus and etc. During the period of pregnancy, mothers or both parents of 6 cases and father of 1 case had histories of genital condyloma acuminata; fathers of 2 cases with histories of immoral sexaul intercourse. Parents of 6 cases denied any history of genetal condyloma and the other 2 cases, no detail information was presented. Post-treatment recurrences were frequently in all cases. 1 case died of severe respiratory distress.
 
Histopathological examination
   All specimens removed by each operative procedure were studied on routine paraffin sections with HE staining.
Detection of HPV-Ag
The HPV-Ags were identified by using the immunoperoxidase staining technique for the demonstration of papillomavirus in paraffin sections. Each case was performed 1~4 times of HPV-Ag detection separately on different specimens.
 
Results
Histopathologic observation
   The morphology of JLP is similar to that of genital condyloma acuminata: complicated papillary arrangement of well-differentiated squamous cell epithelium, parakeratosis, hyperplasia and thickening of the prickle cell layer with koilocytes formation,dyskeratosis,  mitosis appear  in the mid-layer of the epithelium, hyperplasia of the basal cell, chronic inflammatory infiltrates in the dermis.
HPV-Ag detection
   All cases had HPV-Ag positive results: granules with brown or brown-yellow colored were shown in the nuclei of koilocytes.
 
Comment
  JLP is the most common neoplasm of the larynx of childhood and most cases become evident before 5 years of age. The histopathologic similarity between JLP and genital warts has been recognized for many years. In 1923, Ullman transplanted papillomas with cell-free filtrates of JLP to his arm and subsequently to the mucous membrane of a dog, and a viral etiology was first suggested. In 1950's, the viral-like particles within JLP tissues were observed under lectron microscope3. As the application of immunohistochemistry, hybridization and other technique in medical researches, HPV infection being responsible for JLP was confirmed in 1980's. It is now accepted that HPV type 6 and 11, which are usually predominate in anogenital condyloma, are mostcommon in JLP. In the current study, positive results of HPV-Ag staining accords with the conclusion.
  HPV infection in adults is transmitted via sexual contact, but in children it occurs mainly through a nonsexual route. The fact that quite a part of JLP patients had mothers with a history of genital condyloma during pregnancy and the same types of HPV in both diseases led to the hypothesis that HPVs are transmitted from a mother to a newborn at delivery and resultant laryngeal tumor develops after months to years of latency. Newborns are thought to become infected as they pass through the maternal birth canal with HPV infection, secretions containing with the virus are swallowed by the infants and subsequant infection of the child's laryngeal epithelium becomes established. When a pregnant woman with genital condylomas gives childbirth, the hands of the midwives or some equipments may be contaminated by the viginal secretion infected with HPV of the woman. As a result, HPV may be carried into the newbown when the sputum of its mouth cavity is drawn out by hands of the midwives or sucked out by the equipment. Many investigaters suggested that infection acquired intrapartum during fetals pass through an infected birth canal is the principle route of JLP.
  As HPV multiplies locally at the site of entry, though cases of neonates born with congenital perianal condylomata acuminata and laryngeal papillomas being reported dozens of years ago, it was considered formerly as HPV was not blood-borne, so anascending infection reaching the fetus through an unperceived tear in the membraneswas a more likely source of infection in these cases other than transplacental hematogenous infection. More recently, studies provided information about the possibletransplacental transmission of HPV. Some reported a case being delivered by elective cesarean section before the rupture of the membranes developed JLP in the first year of age. Others found HPV DNA in peripheral blood mono-nuclear cells of patients with urogenital HPV infections8. Still others found HPV DNA in both cord and venous blood of infants9. These findings suggested that HPV in those infants probably resultedfrom viral infection before birth through transplacental transmission instead of being acquired from the maternal vaginal secretions or direct contact with the maternal lesions at the time of birth. Though the presence of HPV DNA in cord blood and maternal peripheral blood mono-nuclear cells may not itself indicate the presence of infectious virions, it does suggest a mechanism by which HPV can be transmitted.
  In this study, 6 cases (35.29% ) had positive maternal histories of genital tract  condyloma. Mothers of 3 cases (17.65%) might have HPV infection as fathers of the cases had genital condyloma or immoral sexaul intercourse. Other 8 cases (47.06%) were not presented evidence of parental HPV infections. The positive range of maternalhistory with HPV infection in JLP patients was documented approximately from 30% to 60% in prior literature. Depending on the detection methods used, asymptomaticlatent HPV infection has been reported between 10% and 60% of clinically and histol-ogically normal cervical specimens5 and positive rate may be increased in pregnant women. It may explain the negative maternal history in some JLP cases.
  The possibility that HPVs are transmitted postnatally by close nonsexual contact with an infected person or object cannot be excluded but seems to be unlikely.
  Maternal-fetal transmission of HPV may lead to the development of anogenital condyloma, papilloma of conjunctivae and JLP, but a large majority cases are JLP. So it was speculated by many researchers that HPV must have a predilection for there spiratory epithelium as the disease to be localized in the respiratory tract rather than at other sites. It maybe that HPVs which infected the surface ( without any wounds ) of the fetal body may be eliminated easily before they invade intothe epithelial cells because of washing, erasing, excreting or dropping of the vernix caseosa is also responsible for the condition.
  In conclusion, JLP is a frequent complication in infants of mothers with urogenital condyloma during pregnancy. The transmission of HPV is predominantly occurred duringthe process of birth. HPV may also be transmitted  by other routes during gestation,for instance, ascending infection and transplacental intrauterine transmission. Extensive investigations are clearly required to understand more about the mechanism of maternal-fetal transmission of HPV and find ways for prevention.
   References (Omitted)

 

 

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