HPV infection and clinical profiles in laryngeal diseases. A preliminary study.

PURPOSE: The study analysed the presence of HPV in samples tissue from laryngeal chronic hyperplastic inflammation, with and without pre-neoplastic potential, and from squamous cell carcinoma of the larynx. The aim of this analysis was to evaluate the presence/absence of different types of HPV and their relationship to the clinical profile of the patients studied (habit of smoking and drinking). METHODS: Sixty cases were randomly selected from patients undergoing surgical treatment of the larynx for inflammatory/ neoplastic lesions and of neck nodes. Patients underwent standard clinical workup, comprising medical history and physical examination, panendoscopy, whole-body CT scan (in cancer patients), diagnostic or therapeutic microlaryngoscopy with laryngeal biopsy, and HPV evaluation. RESULTS: The HPV analysis showed an increased risk for heavy smokers of HPV positivity, as well as precancer lesions and cancer. Type 6 and 16 seem to be prevalent in all types of laryngeal mucosa disease, but pre-neoplastic conditions versus cancer seem to show a wider variety of HPV infections while cancer patients are invariably affected by types 6 and 66. Heavy smoking is related to HPV infection likewise alcohol in association with smoking. Advanced T is more associated with HPV positivity. CONCLUSIONS: These data impose a closer follow-up of smokers and pre-neoplastic cases and the utility of the broadspectrum polymerase chain reaction assay in laryngeal dysplastic and cancer lesions. This study may allow to develop biomarkers for early detection or recurrence surveillance, to identify therapeutic targets, and to begin individualization of treatment based on the biology of these tumours. KEY WORDS: HPV infection, Larynx, Laryngeal chronic hyperplastic inflammation, Squamous cell carcinoma.

Endocervical adenocarcinoma in situ presenting in fundal endometrial polyp: the mother of all skip lesions.

A 38-yr-old woman, with a previous history of low grade squamous intraepithelial lesion in the cervix, presented with heavy menstrual bleeding. At hysteroscopy, a fundal polyp was removed from the right cornu which displayed many glands lined by atypical, mitotically active epithelium with features characteristic of endocervical adenocarcinoma in situ (AIS) of intestinal subtype. Subsequent cervical liquid-based cytology and colposcopically directed biopsies revealed no causative lesion, but residual PreservCyt from the ThinPrep vial tested positive for high risk HPV type other than HPV 16 and 18. Further biopsies from the endocervical canal and base of the resected polyp showed intestinal type AIS, while all those from the intervening anterior and posterior endometrial lining exhibited normal endometrium only. Genomic DNA extracted from the endometrial polyp and second set of endocervical biopsies tested positive for HPV 31, an uncommon cause of endocervical glandular neoplasia. Endocervical AIS typically arises in the transformation zone but may be found exclusively in the endocervical canal and rarely as high as 30 mm from the ectocervix. Contiguous spread into the lower uterine segment is known to occur, as are proximate so-called skip lesions. However, finding a 'skip' lesion 80 mm from the transformation zone poses an interesting pathogenetic conundrum as well as a therapeutic dilemma in a young patient desirous of retaining fertility. Issues relating to pathogenesis include necessary metaplasia of the endometrial glandular epithelium to 'susceptible' endocervical type epithelium within the polyp or metastatic implantation of transformed endocervical glandular cells onto the polyp. The current management plan involves regular hysteroscopic surveillance of the uterine cavity.

Squamous intraepithelial lesions arising in benign endocervical polyps: a report of 9 cases with correlation to the Pap smears, HPV analysis, and immunoprofile.

Endocervical polyps are common benign lesions that typically arise in the endocervical canal of women from 40 to 60 years old. The reported incidence of squamous intraepithelial lesion (SIL) occurring in an endocervical polyp is typically less than 1/1,000 (0.1%). We report on 9 cases of SIL arising in otherwise classic benign endocervical polyps; these lesions were from a pool of about 1500 endocervical polyps for an incidence of approximately 0.5%. Five cases were low-grade SIL; of the 4 cases of high-grade SIL, 1 was associated with an invasive squamous cell carcinoma. In 8/9 cases, there was no evidence of SIL on colposcopic examination or biopsy of the remainder of the cervix. There were 12 Pap smears (either concurrent or from 6 mo to 2 yr before the biopsy-proven SIL) taken from the 9 women and most (10/12%-83%) were diagnosed as normal (7), atypical squamous cells of undetermined significance (ASCUS), favor reactive changes (1), or ASCUS (2) whereas the other 2 (17%) smears were diagnosed as low-grade SIL. Human papillomavirus DNA was evident in 7/8 (88%) of the polyps with SIL as determined by in situ hybridization. We conclude that cervical SILs can occur de novo in endocervical polyps, their incidence may be increasing, and, due to their presence in the endocervical canal, where they are much less accessible to sampling with a cytobrush/spatula, may not be evident in the Pap smear.

[Primary study on glycan structure in pathopoiesis mechanism of recurrent respiratory papillomatosis].

OBJECTIVE: To compare the molecular basis difference between recurrent respiratory papillomatosis (RRP) and vocal cord polyp, to analyze the expression of glycan structural genes, and to discuss the pathopoiesis mechanism of RRP. METHODS: The gene expressing profile between the 3 groups papilloma and the vocal cord polyp regarded as normal larynx epithelium were compared using mRNA parallel amplify and the human genome gene expressing microarray. Through cluster analysis, Gene Ontology function gene annotation and path way analysis, the relative gene of RRP and HPV infection were acquired. RESULTS: According to three microarrays results, total 567 expression changed genes related to HPV induce RRP were acquired. A serial change of glycan structure biosynthesis and degradation pathways was significant. The expression of dolichyl-phosphate mannosyltransferase polypeptide 1 (DPM1), asparagine-linked glycosylation 1 homolog (ALG1), fucosyltransferase 8 (FUT8) and alpha-mannosidase 1A (MAN1A) were regulated and beta-hexosaminidase (HEXB), beta1-galactosidase (GLB1), exostoses 1 (EXT1), fucosyltransferase (FUT) reduced expression and heparan sulfate 3-O-sulfotransferase 1 (HS3ST3A1) increased expression. The two related enzymes of the glycosphingolipids which is the main composed of the cell membrane, beta-3-N-acetylglucosaminyltransferase 4 (B3GNT4) and UDP-glucose ceramide glucosyltransferase (UGCG) increase expression, HEXB and GLB1 reduced expression. CONCLUSIONS: The alteration of the coding genes of glycan structure biosynthesis and degradation pathways were significantly and characteristically in pathopoiesis mechanism of RRP. This abnormality may be the beginning of tumor form HPV infection.

Prevalence of and risk factors for gallbladder polyps detected by ultrasonography among healthy Chinese: analysis of 34 669 cases.

BACKGROUND AND AIM: Gallbladder (GB) polyps are tumor or tumor-like projections arising from GB mucosa. Although most polyps are benign, some early GB carcinomas present as polypoid lesions. The diagnosis of GB polyps is relatively easy by ultrasonography. Although numerous studies have investigated GB polyps, few studies have addressed the prevalence of and factors associated with GB polyps for specific ethnic populations. This study analyzes the prevalence and factors associated with GB polyps in a Chinese population who can afford a paid general checkup. METHODS: The prevalence of and risk factors for GB polyps diagnosed by ultrasonography were retrospectively investigated in 34 669 Chinese patients who underwent a general checkup at Chang Gung Memorial Hospital (Taipei, Taiwan) between 2000 and 2003. Demographic, hemogram, serum biochemistry, hepatitis B surface antigen, hepatitis C antibody, and ultrasonography study data was available for all the patients. The correlations between the prevalence of GB polyps and age, sex, body height, body weight, body mass index, hemogram, serum biochemistry, and viral markers were examined for all the patients. RESULTS: Excluding the patients who underwent cholecystectomy, the overall prevalence of GB polyps was 9.5% and highest for middle-aged males. The analyzed risk factors with increased odds ratios (OR) for the development of GB polyps were male sex (OR 0.646, P < 0.0005) and hepatitis B virus surface antigen positivity (OR 1.113, P < 0.0005). Other demographic characteristics and biochemical parameters, including body height, body weight, body mass index, lipid profile, chronic hepatitis C virus infection, and liver function did not correlate with the presence of GB polyps. CONCLUSION: The prevalence of GB polyps among the Chinese in this study is higher than that reported for other populations. Chinese males and other patients with chronic hepatitis B viral infections have a high risk for developing GB polyps.

Cytomegalovirus infection presenting as bronchial polyps in lung transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is the most important opportunistic pathogen in lung transplant recipients and is associated with direct and indirect morbidity. Infection or disease with CMV is often diagnosed through detection of the virus in the blood, culture of bronchoalveolar lavage fluid, or histologic examination of lung tissue obtained on transbronchial biopsy. Endobronchial lesions involving the virus have received little attention, however. METHODS: We reviewed the records of 76 endobronchial biopsies obtained at our institution from January 1999 through October 2004 and performed a detailed examination of the specimens and clinical histories for all patients with biopsy evidence of bronchial CMV infection. RESULTS: We identified three patients with endobronchial CMV infection, manifested in each case as an endobronchial polyp. On histologic examination of the endobronchial biopsy specimens, cells with cytopathic effects characteristic or suggestive of CMV infection were present in two cases, and immunohistochemical staining confirmed the presence of CMV in all three. All patients were clinically well with normal chest X-rays before biopsy. Two of three patients had multiple subsequent episodes of CMV disease. CONCLUSIONS: To our knowledge, this is the first report of endobronchial polypoid CMV disease in lung transplant recipients. Our results suggest that biopsy of endobronchial lesions in pulmonary allografts should be pursued to establish a definitive etiology.

Regression of esophageal papillomatous polyposis caused by high-risk type human papilloma virus.

Esophageal squamous papilloma is an uncommon benign squamous epithelial polypoid tumor and is usually identified as a solitary lesion in the lower esophagus. Chronic mucosal irritation and infection with human papilloma virus (HPV) are two proposed etiologies. However, the natural history of esophageal squamous papilloma is unknown, and whether it can develop to esophageal cancer is also controversial. The authors report a case of esophageal papillomatous polyposis in which the presence of high-risk HPV DNA was proven by type-specific polymerase chain reaction (PCR). The patient was an 83-year-old man referred to our hospital with complaints of nausea and dysphagia. Esophago-gastroduodenoscopy (EGD) was carried out, and diffuse polyposis of the entire length of the esophagus and stenosis in the antrum of the stomach were revealed. Histological examination of the tissue confirmed the diagnosis of squamous papilloma of the esophagus and poorly differentiated adenocarcinoma of the stomach. Furthermore, HPV type-specific PCR was carried out in the biopsied specimens, and HPV type-16 and type-33 were detected. One month after total gastrectomy performed for the treatment of gastric cancer, follow-up EGD was carried out, and complete regression of the esophageal polyps was noted. This case is rare and supports the evidence that esophageal squamous papilloma is caused by infection with HPV. Furthermore, this case also reflects a unique aspect of the natural history of esophageal papillomatous polyposis.

Proliferative activity of benign and neoplastic endocervical epithelium and correlation with HPV DNA detection.

Recent studies have indicated that the use of the MIB-1 immunostaining may be useful in distinguishing endocervical neoplasia from benign nonneoplastic lesions. We sought to investigate this finding further with a specific emphasis on the common benign processes that may result in a nonspecific increase of MIB-1 staining. In this study we quantified the MIB-1 immunostaining in the mucinous endocervical epithelium (n=45) and in tubal metaplasia (n=28) during the proliferative and secretory phases (hormonal influence), in the mucinous endocervical epithelium in cases of cervicitis (inflammation) (n=10), in cases with a history of a recent biopsy (regeneration) (n=15), endocervical polyps (benign growth) (n=8), in the endocervical glands adjacent to a squamous intraepithelial lesion (human papilloma virus [HPV] infection) (n=63), and in in situ and invasive cervical adenocarcinomas (n=30). All cases with increased MIB-1 staining were subsequently tested for the presence of HPV DNA. The range of MIB-1 staining in the benign endocervical epithelium was from 0% to 48% and in the neoplastic epithelium from 25% to 84%. MIB-1 staining below 10% always reflected a benign process and MIB-1 staining higher than 50% was always associated with a neoplasia. Rare benign cases (tubal metaplasia during the proliferative phase, glands adjacent to squamous intraepithelial lesions, and cases with a history of a recent biopsy) had increased MIB-1 index, which overlapped with the neoplastic cases. In conclusion, MIB-1 is a useful marker of endocervical neoplasia, although in rare cases an overlap between benign and neoplastic cases may exist.

[The study of correlation between HPV and vocal cord polyp].

OBJECTIVE: To reveal the correlation between HPV and human vocal cord polyp (vcp). METHOD: Analyzed the morphological changes of 99 vocal cord polyps stained with HE by microscope and 11 specimen by transmission electron microscopy and scanning electron microscopy; Meanwhile, HPV-DNA were detected in 50 vcp by PCR, and then a comparison analysis with the pathological results of vcp was made. RESULT: Koilocytoid cells were observed in 55 of 99 vcp (55.6%); The presence of HPV-DNA were detected in 34 of 50 vcp (68%), HPV-DNA positive rate was 92.9% and 36.4% respectively in 34 cases with koilocyte-like cells expression and 22 cases without koilcyte-like cells expression; there was significant different. The results of electron microscopy agreed with the results under light microscopy except koilocyte-like cell expression. CONCLUSION: There is obvious correlation between HPV and vcp, HPV may play certain role in the occurrence of vcp.

[Herpesviridae and laryngeal neoplasia].

OBJECTIVE: To investigate the relationship between herpesviridae and malignant or benign laryngeal diseases. METHOD: 128 paraffin-embedded laryngeal squamous cell carcinoma and laryngeal epithelium hyperplastic lesions were detected by polymerase chain reaction (PCR) and PCR-ISH for herpesviridae. RESULT: HSV-1 was detected in 10 cases by PCR, among them 3 were laryngeal squamous cell carcinoma (LSCC), 1 was carcinoma in situ(CIS), 4 were laryngeal polyps and 2 were laryngeal keratosis. Except 1 LSCC and 1 CIS 8 of 10 cases were positive while detected by PCR-ISH. In benign diseases, signals were shown from basal layer to superficial cell; in malignant lesions, the signals were scattered in the diseases. CONCLUSION: Most of laryngeal diseases were not related to herpesviridae, but HSV-1 may acts as initiator in the development of a few cases.

MIB-1 immunostaining is a beneficial adjunct test for accurate diagnosis of vulvar condyloma acuminatum.

The histopathologic diagnosis of vulvar condyloma acuminatum is often based on architectural features that are not specific for human papillomavirus (HPV) infection. Because HPV-associated lesions show increased cellular proliferation, the authors evaluated the usefulness of MIB-1 immunostaining as an aid in the differential diagnosis of cases equivocal for condyloma. The MIB-1 immunostaining pattern was correlated with HPV DNA detection in condyloma acuminatum (CON-A; n = 15), "consistent with condyloma" (c/w CON-A; n = 26), fibroepithelial polyp (FEP; n = 14), and squamous papilloma (n = 10). HPV was detected in 100% of the CON-A cases, and all cases demonstrated MIB-1-positive nuclei in the upper two thirds of the epithelial thickness. With this definition of MIB-1 positivity, there was complete concordance between MIB-1 positivity and HPV detection for all cases (kappa = 0.88). Of the cases c/w CON-A, 17 of 26 (65%) were positive for both MIB-1 and HPV, and could be reclassified as CON-A, whereas 35% were identified as an overdiagnosis based on negative results. In addition, two cases of FEP were MIB-1 and HPV positive, and thus were identified as an underdiagnosis. These results suggest significant overdiagnosis of cases equivocal for condyloma, and indicate that MIB-1 immunostaining is a beneficial adjunctive test when the morphologic features are suggestive but not diagnostic for CON-A.

Endocervical reactive atypia: a histologic-cytologic study.

Of 1,500 cervical tissue specimens, 27 cases showed histologic changes of reactive glandular atypia which we defined as endocervical cells with large hyperchromatic, often irregular nuclei, which did not fulfill the criteria for endocervical adenocarcinoma. Eighteen of these 27 cases had preceding or concurrent cervico-vaginal smears. Six of these showed cells which were similar to those seen in histologic sections. The cytologic characteristics of these cells are defined. To determine if atypia is related to inflammatory-regenerative changes, 29 cases of endocervical polyps were examined, of which 11 showed histologic changes of endocervical reactive atypia; 4 showed these changes cytologically as well. Twenty-eight cases of routine hysterectomy specimens were examined, of which 2 cases showed endocervical reactive atypia, which indicated that the atypical changes were indeed reactive. Nine out of 27 cases were associated with hormonal usage. Fourteen cases were associated with squamous intraepithelial lesions or evidence of human papilloma virus. Follow-up of our 27 index cases revealed no progression to adenocarcinoma. These findings indicate that atypia, as we define it, of the endocervix can be due to inflammatory-reparative changes or possibly related to hormonal usage, and permit its separation from precursor lesions of endocervical adenocarcinoma.

Adenovirus and respiratory syncytial virus in chronic sinusitis using polymerase chain reaction.

The aim of this study is to investigate the role of adenovirus and respiratory syncytial virus (RSV) in chronic sinusitis using the polymerase chain reaction (PCR) to assay for the viruses. PCR has proved to be more sensitive and specific than viral cultures and immunoassays in the detection of viruses. Adenovirus and RSV are among the most common viruses to cause upper respiratory tract infections. Sinus mucosa biopsies from 20 patients undergoing endoscopic sinus surgery were sterilely collected. Four specimens (20%) tested positive for RSV by PCR and none tested positive for adenovirus. Only one specimen tested positive for RSV and one for adenovirus by viral culture and immunofluorescence. Bacterial cultures tested positive in 40% of the 20 specimens. PCR can be used to detect RSV in patients with chronic sinusitis and PCR is more sensitive than viral culture and immunofluorescence techniques on sinus polyps and mucosa.