Hip fractures are preventable: a proposal for osteoporosis screening and fall prevention in older people.

Osteoporosis is highly prevalent but underdiagnosed and undertreated in Hong Kong. Fragility fractures associated with osteoporosis often result in loss of independence and increased mortality for home-dwelling patients, imposing a high socio-economic burden on society. This issue requires urgent attention given the rapid growth of the elderly population in Hong Kong by approximately 4.3% each year. To address this situation, a group of experts convened to discuss practical ways to reduce the burden of fractures and formulated three recommendations: first, all men (aged ≥70 years) and women (aged ≥65 years) should receive universal dual-energy X-ray absorptiometry assessment for osteoporosis. Second, all men (aged ≥70 years) and women (aged ≥65 years) with a fracture-risk assessment-derived 10-year risk (hip fracture with bone mineral density) ≥3% should receive ≥3 years of anti-osteoporotic treatment. Third, comprehensive structured assessment (including dual-energy X-ray absorptiometry) should be conducted in older patients with a history of falling. By implementing these recommendations, we estimate that we could prevent 5234 hip fractures in 10 years, an annual incidence reduction of approximately 7%, and save HK$425 million in direct medical costs plus substantial indirect savings. Ample clinical and cost-effectiveness data support these recommendations, and studies in Hong Kong and abroad could serve as models on how to implement them. We are confident that by applying these recommendations rigorously and systematically, a significant reduction in hip fractures in Hong Kong is achievable.

Chemoradiation and adjuvant chemotherapy in cervical cancer.

PURPOSE: Radiotherapy is the standard treatment for locally advanced cervical cancer, but treatment results remain disappointing, particularly for women with bulky central disease. We investigated the role of concurrent chemoradiation and adjuvant chemotherapy in a randomized trial. PATIENTS AND METHODS: Two hundred twenty patients with bulky stage I, II, and III cervical cancer were randomized to receive either standard pelvic radiotherapy or chemoradiation (epirubicin 60 mg/m(2)) followed by adjuvant chemotherapy with epirubicin 90 mg/m(2) administered at 4-week intervals for five additional cycles. RESULTS: Fifty-nine patients have relapsed, with a median follow-up duration of 77 months. Patients who received epirubicin radiation therapy showed a significantly longer disease-free (P =.03) and cumulative survival (P =.04). Patients who received radiation alone had significantly more distant metastasis than those who received chemoradiation (P =.012). There was no difference in long-term local tumor control (P =.99). CONCLUSION: Survival benefit has been demonstrated in patients treated with chemoradiation followed by adjuvant chemotherapy with epirubicin as compared with patients treated with standard pelvic radiotherapy alone.

Tumor control probability of nasopharyngeal carcinoma: a comparison of different mathematical models.

PURPOSE: Radiation dose and tumor volume are factors known to affect the local control of a given type of tumor. Local tumor control is a major factor to consider when a treatment plan is evaluated. This article reports the correlation between tumor control probability, dose, and volume in a retrospective study of 142 patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The tumor volume was outlined and calculated from a computed tomographic scan. Patients were categorized according to tumor volume and radiation dose received in treatment. Local control rate was calculated for each category by the Kaplan-Meier method. Mathematical models were fitted to correlate the local control rate, dose, and volume. Both empirical and mechanistic approaches were attempted; the former included logistic models with two and three parameters, and the latter, the formulation from Brenner and Bentzen with a radiobiological basis. RESULTS: Brenner's model estimated alpha at 0.041 Gy(-1) with 95% confidence limits (-0.032, 0.113) Gy(-1). The volume dependent constant h was estimated at 0.160 cm(-3) with 95% confidence limits (-0.729, 1.048) cm(-3). The Pearson correlation coefficient was 0.64. The magnitude and sign of the fitted parameters were reasonable and consistent with reported clinical experience. The other models were fitted with slightly better goodness of fit (r = 0.65 - 0.68), but with less interpretable parameters. CONCLUSION: Brenner's model is considered appropriate for a description of the dose and volume effect on the local control of the NPC. It could be used in combination with normal tissue complication probability for treatment plan evaluation to optimize treatment results.

The effect of interruptions and prolonged treatment time in radiotherapy for nasopharyngeal carcinoma.

PURPOSE: The effect of interruptions and prolonged overall treatment time in radiotherapy for nasopharyngeal carcinoma and the significance of timing of interruption was investigated. METHODS AND MATERIALS: Treatment records of 229 patients treated with continuous course (CC) and 567 patients treated with split course (SC) radiotherapy for nonmetastatic NPC were reviewed. Overall treatment time without inclusion of time for boost was calculated. Treatment that extended 1 week beyond scheduled time was considered prolonged. Outcome in patients who completed treatment "per schedule" were compared with those who had "prolonged" treatment. Because of known patient selection bias between CC and SC, patients on the two schedules were analyzed separately. Multivariate analysis was performed for patients on SC. Total number of days of interruption, age, sex, T and N stage, and the use of boost were tested for the whole SC group. Analysis on the effect of timing of interruption was performed in a subgroup of 223 patients on SC who had a single unplanned interruption. Timing of interruption, either before or after the fourth week for the unplanned interruption, was tested in addition to the other variables in multivariate analysis for this subgroup of SC. RESULTS: Twenty-seven (11.8%) patients on CC and 96 (16.9%) patients on SC had prolonged treatment. Patients on SC who had prolonged treatment had significantly poorer loco-regional control rate and disease free survival when compared with those who completed radiotherapy per schedule (p = 0.0063 and 0.001, respectively, with adjustment for stage). For CC, the effect of prolonged treatment on outcome was not significant. The small number of events for patients on CC probably account for the insignificant finding. The number of days of interruption was confirmed as prognostic factor, independent of T and N stages, for loco-regional control and disease-free survival in multivariate analysis for SC. The hazard rate for loco-regional failure increased by 3.3% for each day of interruption. The timing of interruption, at the beginning or towards end of treatment, did not significantly alter outcome. CONCLUSION: Interruptions and prolonged treatment adversely affect outcome in radiotherapy for NPC and the effect of repopulation was confirmed. Every effort should be made to keep treatment on schedule and interruptions for whatever reasons should be minimized.

Sensorineural hearing loss in patients treated for nasopharyngeal carcinoma: a prospective study of the effect of radiation and cisplatin treatment.

PURPOSE: The pattern of sensorineural hearing loss (SNHL) after primary treatment for nasopharyngeal carcinoma (NPC) was studied, and the effect of cisplatin, radiotherapy does, and fractionation were evaluated. METHODS AND MATERIALS: One hundred thirty-two patients, 227 ears, and 1100 audiogram reports were analyzed. Radiotherapy dose ranged from 59.5 to 76.5 Gy. Fifty-two patients received preirradiation cisplatin, total dose 100-185 mg/m(2). Serial postirradiation bone conduction thresholds at 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz were compared with pretreatment thresholds at respective frequencies. Increase of at least 15 dB was considered as significant and was further grouped as transient or persistent SNHL. Univariate and multivariate analyses were performed to identify predicting factors for persistent SNHL. RESULTS: At median follow-up of 30 months, 24.2% of ears developed persistent SNHL. High frequency was more affected than low frequencies, 22 vs. 5.3%. Males were more affected than females, 29.4 vs. 15.5%, p = 0.0132. Incidence of persistent SNHL increased with age, with 0, 17.2, and 37.4% of patients aged under 30, between 30-50 and over 50 affected, respectively, p = 0.0001. High incidence was found in patient with postirradiation serous otitis media (SOM), 46.9%. Chemotherapy with cisplatin and radiation dose or fractionation had no significant effect. Multivariate analysis confirmed age, sex, and postirradiation SOM as significant prognostic factors for persistent SNHL. CONCLUSIONS: Transient and persistent SNHL occurred after radiotherapy, more commonly affecting high frequency. A low dose of preirradiation cisplatin did not increase the risk. A dose fractionation effect of radiotherapy was not confirmed in this study.

Nephrotic syndrome associated with angiofollicular lymph node hyperplasia.

A women presented at the age of 22 with anemia, hepatosplenomegaly, polyclonal hypergammaglobulinemia and a mediastinal shadow. At thoracotomy she had enlarged mediastinal lymph nodes which displayed histological features typical of angiofollicular hyperplasia. Marrow plasmacytosis was present. She developed diabetes mellitus at the age of 29 yrs after she had received oral steroid treatment for one year. The nephrotic syndrome supervened another year later. Her kidneys were enlarged before the onset of diabetes. The glomerular changes included a marked increase of mesangial matrix and segmental hypercellularity. The association of the nephrotic syndrome and angiofollicular lymph node hyperplasia is extremely rare and their interrelation remains enigmatic.

Use of prophylactic antibiotics in patients with carcinoma of the cervix receiving intracavitary radium insertion.

The efficacy was studied of prophylactic antibiotics in preventing febrile morbidity in patients with carcinoma of the cervix undergoing intracavitary radium insertions. Of 93 consecutive patients who had completed external irradiation and two intracavitary radium insertions, 63 (67.74%) had fever over 37.5 degrees C and 19 (20.43%) had fever over 38 degrees C during radium insertion when prophylactic antibiotics were not given. When 3 gm cefoxitin was given over 24 hrs in divided doses as prophylaxis, 39 (41.93%) had fever over 37.5 degrees C and 8 (8.60%) had fever over 38 degrees C. The difference was found to be statistically significant for fever over 37.5 degrees C (p < 0.001) and fever over 38 degrees C (p < 0.05). There was no difference in the duration of fever in the two groups, but the use of antibiotic prophylaxis apparently decreased the need for subsequent therapeutic antibiotics from 13.98% to 4.30%. No difference in the febrile incidence was found when considering the size of the cervical tumour, the stage of the disease, or whether it was a first or second radium insertion, or whether the patient had her menopause already. Prophylactic antibiotics were also found to be more effective in preventing febrile morbidity over 37.5 degrees C in those receiving adjuvant chemotherapy as compared to the general study group (p < 0.025). We concluded that the use of prophylactic antibiotics has beneficial effect in decreasing febrile episodes during the period the radium was inserted, as well as in reducing subsequent need for therapeutic antibiotics, while its use in immunocompromised patients who are prone to sepsis may also be of advantage.

Early changes of auditory brain stem evoked response after radiotherapy for nasopharyngeal carcinoma--a prospective study.

A prospective study of the effect of radiotherapy for nasopharyngeal carcinoma on hearing was carried out on 49 patients who had pure tone, impedance audiometry and auditory brain stem evoked response (ABR) recordings before, immediately, three, six and 12 months after radiotherapy. Fourteen patients complained of intermittent tinnitus after radiotherapy. We found that 11 initially normal ears of nine patients developed a middle ear effusion, three to six months after radiotherapy. There was mixed sensorineural and conductive hearing impairment after radiotherapy. Persistent impairment of ABR was detected immediately after completion of radiotherapy. The waves I-III and I-V interpeak latency intervals were significantly prolonged one year after radiotherapy. The study shows that radiotherapy for nasopharyngeal carcinoma impairs hearing by acting on the middle ear, the cochlea and the brain stem auditory pathway.

Analysis of Epstein-Barr virus in localized nasopharyngeal carcinoma tumors.

BACKGROUND: An f variant of Epstein-Barr virus (EBV) appears associated with nasopharyngeal carcinoma (NPC) in Southern Chinese. Early diagnosis of the tumor allows the detection of some localized tumors. METHODS: A polymerase chain reaction (PCR) assay for genotyping EBV was used to evaluate the presence of the virus in NPC biopsies of local tumors of eight Chinese patients. RESULTS: The f variant was detected in the nasopharynx of seven of eight patients. The f variant was present in equal frequency in the "normal" and tumor regions. CONCLUSIONS: Examination of localized NPC tumors by the PCR genotyping assay revealed EBV was present on the tumor side of the nasopharynx in greater quantities than the "normal" side in seven of eight patients studied. Concurrent infection with both the prototype F and f variant was observed in two of the eight patients investigated.

Evaluation of cervical nodal necrosis in nasopharyngeal carcinoma by computed tomography: incidence and prognostic significance.

PURPOSE: The purpose was to study the prognostic value of contrast-enhanced computed tomography (CT) nodal necrosis in nasopharyngeal carcinoma. PATIENTS AND METHODS: One hundred sixty-one patients with newly diagnosed nasopharyngeal carcinoma and nodal metastases were reviewed. Forty patients also received cisplatin-based neoadjuvant chemotherapy in addition to radiotherapy. Nodal necrosis was defined as presence of hypodense areas in more than 33% of the node. Nodal response rate to chemotherapy, overall nodal control rate, local control rate, distant failure rate, overall relapse-free survival rate, and overall and cause-specific survival rates were compared between patients with and without nodal necrosis. Multivariate analysis was also performed. RESULTS: The incidence of nodal necrosis was 22.9%. Overall nodal response rates to chemotherapy were 88.9% (8/9) in patients with nodal necrosis and 74.2% (23/31) in those without. No significant differences in nodal control rate, local control rate, distant failure rate, and overall and cause-specific survival rates were found. Five-year overall relapse-free survival rate was lower in patients with cervical nodal necrosis (36%) as compared with those without (53%, p = .04). Multivariate analysis, however, did not confirm cervical nodal necrosis to be an independent prognostic factor. CONCLUSIONS: Presence of nodal necrosis in nasopharyngeal carcinoma does not affect nodal response to chemotherapy and nodal control by radiotherapy with or without chemotherapy. Cervical nodal necrosis does not appear to be an independent factor in predicting treatment outcome. Further studies to correlate nodal density with oxygenation status as well as tumor cell kinetics are warranted.

Retropharyngeal lymphadenopathy in patients with nasopharyngeal carcinoma: a computed tomography-based study.

BACKGROUND: The purpose of this study was to investigate the incidence and prognostic value of retropharyngeal lymphadenopathy in nasopharyngeal carcinoma patients using contrast enhanced computed tomography (CT). METHODS: From January 1989 to December 1991, 364 patients with newly diagnosed nasopharyngeal carcinoma without distant metastasis had a baseline CT performed. All patients had radiotherapy as their primary treatment. Eighty-seven patients also received neoadjuvant chemotherapy for locally advanced disease. All patients with clinical N0 disease had prophylactic lymph node irradiation. The contrast enhanced CT given prior to all treatment was evaluated for the presence of retropharyngeal lymphadenopathy. Criteria for involved lymph nodes included a lymph node size of 10 mm or more, the presence of central necrosis within the lymph node, or the presence of a contrast enhancing rim. RESULTS: The incidence of retropharyngeal lymphadenopathy was 29.1%. A higher incidence of retropharyngeal lymph node involvement was observed in Ho's T2/T3 disease compared with T1 disease, and a higher incidence was also found in patients with cervical lymph node disease compared with those with clinical N0 disease. No significant differences in relapse free survival rates, local control rates, lymph node control rates, or distant failure rates were observed between patients with or without retropharyngeal lymphadenopathy after adjusting for T and N classifications. In 134 patients with clinical N0 disease, retropharyngeal lymphadenopathy was found in 21 patients, whereas 113 had no evidence of retropharyngeal lymphadenopathy. However, no significant difference in treatment outcome was observed between the two groups. CONCLUSIONS: Using CT imaging, the presence of retropharyngeal lymphadenopathy in patients with nasopharyngeal carcinoma does not appear to affect the prognosis. In patients with clinical N0 disease, the identification of retropharyngeal lymphadenopathy based only on CT imaging is not sufficient evidence for an N1 classification.

Prognostic value of paranasopharyngeal extension of nasopharyngeal carcinoma. A significant factor in local control and distant metastasis.

BACKGROUND: This study was conducted to evaluate the prognostic value of paranasopharyngeal extension in local control and distant metastasis in patients with nasopharyngeal carcinoma. METHODS: Three hundred and sixty-four patients with newly diagnosed nasopharyngeal carcinoma without distant metastasis were reviewed. Patients were staged according to Ho's staging system. Using a semiquantitative method, tumor extension into the paranasopharyngeal space was graded as: 0: no extension; 1: extension to the retrostyloid space; 2: extension to the prestyloid space; and 3: extension to the anterior part of the masticator space. All patients received radiotherapy as primary treatment. Median follow-up time was 45 months (range, 4.7 to 76.5 months). Relapse free, local relapse free, and distant metastasis free survival were estimated using the Kaplan-Meier method. Cox regression was also performed to adjust for prognostic factors. RESULTS: The incidence of paranasopharyngeal extension was high (72.5%). Of these patients, 65.5% had Grade 2 or 3 extension. The 5-year relapse free survival rates for Grade 0, 1, 2, and 3 extension were 76%, 70%, 46%, and 43%, respectively. The main difference was between Grade 0/1 and Grade 2/3 extension, the latter having a lower 5-year local control rate (86% in Grade 0/1 vs. 72% in Grade 2/3; P < 0.0001) and distant metastasis free survival rate (87% in Grade 0/1 vs. 68% in Grade 2/3; P = 0.0002). Multivariate analysis showed that Grade 2/3 paranasopharyngeal extension was an independent factor in predicting overall relapse, local relapse, and distant metastasis. Advanced T classification (T3) was another independent factor in predicting overall and local relapse, whereas advanced N classification (N3) was another independent factor in predicting overall relapse and distant metastasis. CONCLUSIONS: Extensive paranasopharyngeal extension (Grade 2/3) was an independent prognostic factor associated with poorer treatment outcome, both in local control and distant metastasis. Ho's T2 disease should be further subclassified into T2a and T2b, which include Grade 0/1 and Grade 2/3 paranasopharyngeal disease, respectively.

Serum squamous cell carcinoma antigen in the monitoring of radiotherapy treatment response in carcinoma of the cervix.

In this study, squamous cell carcinoma antigen (SCC) was detected in 96 of 157 patients with squamous cell carcinoma of the cervix and the percentage of patients with raised SCC levels increased with the stage of disease (P less than 0.01). The use of serial SCC assays and cervical biopsy histology during the course of radiotherapy to predict tumor response to irradiation was assessed. In patients who were given external irradiation before intracavitary radium, a high SCC level or the presence of viable tumor cells in the biopsy was found to be of no predictive value. However, at completion of radiotherapy, i.e., after intracavitary radium application, patients with persistently high SCC levels had a significantly higher incidence of residual tumor than patients whose SCC levels returned to normal (P less than 0.01). In 60% of patients with a persistently high SCC level, viable tumor was found in the cervical biopsy at the end of radiotherapy. On the other hand, only 5.4% of patients whose SCC level returned to normal had residual tumor.

The relationship between COLI A1 polymorphisms (Sp 1) and COLI A2 polymorphisms (Eco R1 and Puv II) with bone mineral density in Chinese men and women.

Polymerase chain reaction was used to amplify across variable restriction sites of the COLI A1 and COLI A2 genes that encode the alpha 1 and 2 subunits of type I collagen. The relationship between these polymorphisms and bone mineral density (BMD) was studied in 683 Chinese men and women. In 100 men and women, COLI A1 Sp1 polymorphism was not found, which was consistent with other previous studies in Asian populations. However a statistically significant relationship was observed between COLI A2 Eco R1 and Puv II genotypes among the Chinese men studied. The mean BMD was consistently lower in men of the EE and PP genotype (P < 0.05 by analysis of variance [ANOVA]) than in men of the ee and pp genotypes. However, no association between BMD and the Eco R1 or Puv II genotypes was observed in Chinese women (P > 0.05 by ANOVA). We conclude that the COLI Al Sp1 binding site is absent in Hong Kong Chinese, whereas the COLI A2 Eco R1 and Puv II genetic polymorphisms may be associated with the BMD of elderly Chinese men.

Transcription of BamHI-A region of the EBV genome in NPC tissues and B cells.

Analysis by Northern blotting and sequencing of cDNA clones from a transcription library of a tumor biopsy from a nasopharyngeal carcinoma (NPC) patient showed that the BamHI-A region of the Epstein-Barr virus genome is abundantly and regularly transcribed in tumor tissues from NPC patients. The transcription occurred in a rightward direction terminating between coordinates 160,965 and 160,995, where two polyadenylation sites are located. Rightward transcription of this region also occurred in B lymphoid cells harboring the viral genome, albeit at a lower level than in the tumor tissues. Differential splicing yields a family of related transcripts displaying at least four splicing patterns. Different promoters may be utilized, further contributing to the diversity of this family of transcripts. A 2.8-kb unspliced transcript present in B95-8 cells was probably initiated from a TATA box located in position 158,204, while the other transcripts may utilize other promoters localized to other regions. All the transcripts encompass a putative open reading frame, BARFO, which is predicted to encode a basic protein of about 20 kDa. It shares 40% colinear amino acid sequence homology with the DNA binding region of a transcription factor, ICP4, specified by herpes simplex virus.

4-epidoxorubicin in recurrent cervical cancer.

Thirty-eight patients with histologically proven recurrent cervical cancer were treated with epirubicin, an analogue of anthracycline. There were eight complete responders and ten partial responders. The overall response rate was 47.8%. The survival duration of the responders was significantly longer than that of the nonresponders. The optimal dose of epirubicin has yet to be determined. The dosage of 120 mg/m2 was well tolerated. The role of epirubicin as an adjuvant chemotherapeutic agent in the treatment of cervical cancer was discussed.

Nasopharyngeal carcinoma and lymphoinfiltration.

Originally referred to as 'lymphoepithelioma', undifferentiated and poorly differentiated nasopharyngeal carcinoma (NPC) tissues showed intense lymphoinfiltration. In a study of cryosections from 15 NPC tissues, we found that infiltrating lymphoid elements were comprised predominantly of lymphocytes, but plasma cells, follicular dendritic cells, and eosinophils were also commonly seen. Subpopulations of lymphocytes having the same phenotypes tend to aggregate, forming clusters or secondary follicles in stromatous tissues. The tumor areas were mainly infiltrated by T cells. Tumor cells and/or apparently normal epithelium in the paratumorous areas frequently expressed CD21, CD23, CD40 and a B lymphocytes carcinoma cross-reacting antigen (BLCa), all of which are involved in B cell activation and proliferation. CD21 and BLCa were strongly expressed near the surface of both squamous and columnar epithelium by those epithelial cells which are at advanced stage of differentiation, while CD40 was expressed by epithelial cells at earlier stages of differentiation located at or near the basement membrane. CD23 was mainly expressed by columnar cells and basal cells underlying squamous epithelium, but not, or weakly so, by flattened squamous cells or reserve cells underlying columnar epithelium. The large majority of tumor cells expressed CD40 and BLCa. A substantial proportion of them also expressed CD23, but the tumor cells were not reactive for CD21. Despite eosinophilic infiltration, IL-6 was not detected in tumor tissues. IL-1 was, however, detected in abundance in the cytoplasm of follicular dendritic-like cells and in the intercellular spaces in tumor areas and surrounding stromatous tissues. The immunobiology of NPC is discussed in the light of these observations.

Long term results of radioactive gold grain implantation for the treatment of persistent and recurrent nasopharyngeal carcinoma.

BACKGROUND: Brachytherapy is useful for the reirradiation of nasopharyngeal carcinoma. In the current study, the long term treatment results of permanent radioactive gold(198) grain interstitial implantation in patients with persistent and recurrent nasopharyngeal carcinoma were reviewed. METHODS: Gold grain implantation was performed under direct vision with a split palate approach to provide 60 grays (Gy) 0.5 cm away from the plane of implantation. Between August 1986 and May 1999, 106 patients were treated with gold grain implantation (45 patients for persistent disease, 53 patients for first recurrence, and 8 patients for second recurrence in the nasopharynx). All patients had histologically proven disease by biopsy before undergoing implantation. RESULTS: Patients with persistent disease and those with first recurrence did well with the gold grain implantation. The 5-year local control rates for patients with persistent disease, first recurrence, and second recurrence in the nasopharynx were 87.2%, 62.7%, and 23.4%, respectively (P = 0.0004). The 5-year metastasis free survival rates were 68.1%, 60.3%, and 40%, respectively, for the 3 groups (P = 0.048). The overall survival rates at 5 years for the 3 groups were 79.1%, 53.6%, and 42.9%, respectively (P = 0.0047). Patients with computed tomography evidence of disease extension outside the nasopharynx had a lower local control rate compared with patients whose disease was confined to the nasopharynx (5-year local control rate of 52% vs. 72.3%; P = 0.031). The size of the lesion was not found to be an independent prognostic factor for local control after implantation. Multivariate analysis showed only an indication for implantation (persistent disease, first recurrence, and second recurrence) to be a significant prognostic factor for local control. Complications attributed to gold grain implantation included headache, palatal fistula, and mucosal radiation necrosis at the site of implantation, and were reported to occur in 28.3%, 18.9%, and 16%, respectively, of patients. CONCLUSIONS: For selected patients with disease confined to the nasopharynx, gold grain implantation is an effective salvage treatment for persistent and recurrent nasopharyngeal carcinoma.

Epstein-Barr virus carriage by nasopharyngeal carcinoma in situ.

We studied the distribution of the EBV genome in tumour biopsies obtained from 42 patients with poorly differentiated or undifferentiated nasopharyngeal carcinoma (NPC) and 3 patients with well-differentiated NPC. Six carcinoma in situ (CIS) foci were seen in 5 tumour specimens. By in-situ hybridization, multiple copies of the EBV genome were detected in some of the tumour cells in 3 CIS lesions involving the full thickness of the mucosal epithelium, but without microinvasion, while the viral genome was present in the majority of the tumour cells contained in another 3 CIS lesions with microinvasion. In agreement with previous findings, poorly differentiated and undifferentiated carcinomas regularly carried the viral genome, the number of copies of which was similar to that seen in CIS, while some, but not all, of the tumour cells of the well-differentiated histological type carried the virus. The viral genome was otherwise rarely detected in other areas of the mucosal epithelium and, where present, the viral carriage was confined to a few epithelial cells, in which the viral genome contents were markedly lower than in tumour cells. These results suggest that EBV may first become associated with NPC at an early stage of the disease shortly after the tumour has been initiated.