Fuju Chang

Infectious agents in the etiology of esophageal cancer.

Extensive epidemiological and experimental studies have suggested that some chemical agents, nutritional deficiencies, and physical factors are associated with the development of esophageal cancer (EC). Recent evidence also suggests an etiologic role of certain microorganisms in esophageal carcinogenesis either by producing carcinogens or promotors or by acting directly on the host cells. The mutagenic and carcinogenic effects of several fungi and bacteria isolated from the grains and foodstuffs in high-risk areas have been shown by in vitro and in vivo studies. Certain viruses, e.g., human papillomavirus, herpes simplex virus, cytomegalovirus, and Epstein-Barr virus, have been implicated in the pathogenesis of a variety of human cancers, and all of them are known to produce tumors in animals and cell transformation in vitro. These viruses also have been shown to infect the esophageal epithelium. Therefore, although many of the key issues of their mechanisms of action are unclear as yet, they should be considered potential etiologic agents of EC. The present review summarizes the data available on the etiology of EC, emphasizing the current evidence implicating an etiologic role of microorganisms in the pathogenesis of this malignancy.

An interlaboratory study to determine the presence of human papillomavirus DNA in esophageal carcinoma from China

Esophageal‐carcinoma samples originating from the high‐incidence area of China were tested in 2 different laboratories, each using a different degenerate PCR approach. Results confirmed the notion that none of the PCR approaches available for HPV‐DNA detection today, is optimal for detecting all known HPV types at equal sensitivity and specificity. In combining results obtained in both laboratories, HPV DNA was demonstrated in 20/117 (17.1%) esophageal‐carcinoma samples analyzed. HPV DNA was detected in 3/70 (4.3%) diagnostic biopsies, 7/23 (30.4%) surgical specimen and 10/24 (41.6%) cytological scrapings originating from the entire surface of the esophagus. Mucosotropic HPV types were present in 7/117 (6%) samples, only 3 being of the high‐risk types (HPV 16, 18, 33). Other mucosal types found were HPV 6, 11, 13, 53 and 54. Cutaneous HPV types were present in 14/117 (12.0%) samples. HPVs 20 and 38 were present in 3 (2.6%) of the total samples and, in each case, together with another HPV type within one lesion. Two putative new HPV types, DL347 and DL 369, were identified. Int. J. Cancer 81:225–228, 1999.

Screening for human papillomavirus infections in esophageal squamous cell carcinomas by in situ hybridization

Background. Infections with specific types of human papillomavirus (HPV) have been closely linked with human squamous cell carcinomas, those of the anogenital tract in particular. Increasing number of reports also suggest that HPV infection could be a risk factor for esophageal cancer. However, most of the previous studies on HPV involvement in esophageal carcinomas have included only small numbers of biopsy specimens, thus necessitating additional studies based on extensive series of esophageal samples.

Human papillomavirus infections in the respiratory tract.

The papillomaviruses are small DNA vi- matous, and verrucous lesions of the squaruses that belong to the family Papovaviridae. mous epithelium.4~“-8 HPV infections have They are ubiquitous and affect both man and been reported in a number of body sites, inanimals, including dogs, cats, cattle, sheep, cluding the anogenital tract, urethra, skin, larrabbits, and other species.le4 The virion con- ynx, tracheobronchial mucosa, nasal cavity/ sists of a central core of circular, double- paranasal sinuses, oral cavity, esophagus, and stranded DNA with a nucleotide length of conjunctiva.6-25 HPV involvement in a variety about 7.9 kb, enclosed within an outer capsid of benign lesions of the aerodigestive tract, inof viral proteins.le3 The viral capsid is com- cluding those of the oral mucosa (squamous posed of 72 subunits (capsomeres) arranged in cell papilloma/condyloma, verruca, focal epia symmetrical, 20-sided (icosahedral) pattern thelial hyperplasia, lichen planus, and leukothat gives the individual virion an almost plakia) as well as inverted papilloma of the spherical shape on electron microscopy. Al- nasal cavity and paranasal sinuses, and respithough the papillomaviruses share group- ratory papillomatosis (eg, laryngeal papillospecific antigens, they can be classified ac- mas), has been demonstrated by histopathocording to their host range and the degree of logical, ultrastructural, immunohistochemihomology of their nucleic acids. Any new iso- cal, and DNA hybridization studies.7-25 Of the late that exhibits less than 50% homology known HPV types, HPV 1,2,4,6, 7,11,13,16, (tested by reassociation in the liquid phase] 18, 30, 32, 40, and 57 have been detected in with existing members is designated as a new these lesions.7-25 Of these, HPV 11 was origitype and numbered in order of discovery. If nally cloned from a recurrent lesion of larynthe homology is higher than 5O%, they are geal papillomatosis,21 HPV 13 and 32 from foconsidered subtypes.le3 So far, more than 66 cal epithelial hyperplasia of the oral cavtypes of human papillomaviruses (HPV) have ity, 22,23 HPV 30 from a laryngeal carcinoma,z4 been identified,5 and the number is likely to and HPV 57 from an inverted papilloma of the increase in the future. maxillary sinus.25 Papillomaviruses are epitheliotrophic and primarily affect the skin and mucous membranes of the genitourinary and upper aerodigestive tracts, inducing hyperplastic, papillo

Detection of Human Papillomavirus Infections in the Male Sexual Partners of Women Attending an STD Clinic in Bologna

A series of 65 male sexual partners of 65 women attending an STD clinic in Bologna, Italy for examination and treatment of genital human papillomavirus (HPV)-infections during 1990–1991, were examined using peniscopy and surgical biopsy, the latter being analysed by light microscopy, in situ hybridization (ISH) and polymerase chain reaction (PCR) for HPV DNA. A detailed medical and sexual history was recorded from all men. Of the 65 men, 17 (26.2%) gave a history of a previous STD. The male partners with previous genital condylomata (14, 21.5% of men) were significantly associated with the detection of HPV DNA in the current lesions; 21.4% (3 of 14) and 10.2% (5 of 51) in those with and without previously treated condyloma, respectively. On colposcopy, 63 (96.9%) men presented with an abnormal pattern, the vast majority (49 of 65, 75.4%) showing an acetowhite lesion, and only 12 (18.5%) lesions being classified as condyloma acuminatum. HPV DNA was found, however, in only 4 of 12 (33.3%) condylomas by ISH and PCR, and in 4 of 49 (8.2%) and 6 of 49 (12.2%) acetowhite lesions by ISH and PCR, respectively. In a total of 41 (63%) patients, the biopsy was classified as non-HPV on light microscopy. HPV DNA detection rate was significantly higher in all morphologically HPV-suggestive lesions, compared with the non-HPV where ISH was invariably negative. PCR, however, disclosed HPV DNA in 4 of 41 (9.8%) cases. PIN (I or II) was present in 6 of 65 (9.2%) men. HPV DNA detection rate increased in parallel with the increasing grade of lesion, both HPV 16-positive cases containing a PIN lesion. Altogether, HPV DNA was found by ISH in 8 of 65 (12.3%) biopsies, and PCR amplification increased the detection rate by only two cases. HPV DNA was never present in men with only a single sexual partner, but increased significantly when the number of partners was increased, being highest (27.3%, 3 of 11) in those reporting 11–20 partners. HPV detection rate was lowest in those men whose partner had a flat condyloma, but significantly higher in those who presented with condyloma acuminatum (40%, 2 of 5), or HPV-CINI and II lesions. Of interest was the finding that HPV DNA was never demonstrated in the men whose partner had only vaginal HPV lesions. Peniscopy is an applicable means of finding the abnormal patterns remaining undetectable by the naked eye, but because of its limited resolution, it is not a conclusive diagnostic tool capable of differentiating HPV- from non-HPV-lesions.

Detection of human papillomavirus (HPV) in genital warts and carcinomas by DNA in situ hybridization in Chinese patients

A series of 51 genital biopsies from normal epithelium, condylomata acuminata, leucoplakia and squamous cell carcinoma from Chinese male and female patients were analysed for the presence of human papillomavirus (HPV) types 6, 11, 16 and 18 by DNA in situ hybridization. All of the nine genital condyloma acuminata were positive for HPV DNA, in which HPV 6 was found in six cases, HPV 11 in two cases and HPV 18 in one case. Twelve out of the 21 cases (57.1% of the total) of cervical squamous cell carcinoma were shown to contain HPV DNA; HPV 16 was found in nine cases, HPV 18 in two cases and HPV 16/18 in one case. Present results support the earlier concept that HPV 6/11 are closely associated with benign genital lesions, and HPV 16/18 are mostly confined to higher grade of intra‐epithelial neoplasias and carcinoma.