Cancer in a population-based cohort of men and women in registered homosexual partnerships.
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Cancer patterns among broad populations of homosexual men and women have not been studied systematically. The authors followed 1,614 women and 3,391 men in Denmark for cancer from their first registration for marriage-like homosexual partnership between 1989 and 1997. Ratios of observed to expected cancers measured relative risk. Women in homosexual partnerships had cancer risks similar to those of Danish women in general (overall relative risk (RR) = 0.9, 95% confidence interval (CI): 0.6, 1.4), but only one woman developed cervical carcinoma in situ versus 5.8 women expected (RR = 0.2, 95% CI: 0.0, 0.97). Overall, men in homosexual partnerships were at elevated cancer risk (RR = 2.1, 95% CI: 1.8, 2.5), due mainly to human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (RR = 136, 95% CI: 96, 186) and non-Hodgkin's lymphoma (RR = 15.1, 95% CI: 10.4, 21.4). Anal squamous carcinoma also occurred in excess (RR = 31.2, 95% CI: 8.4, 79.8). After exclusion of Kaposi's sarcoma, non-Hodgkin's lymphoma, and anal squamous carcinoma, no unusual cancer risk remained (RR = 1.0, 95% CI: 0.8, 1.3). With anal squamous carcinoma and HIV/AIDS-associated cancers as notable exceptions in men, cancer incidence rates among homosexual persons in marriage-like partnerships are similar to those prevailing in society at large. (+info)
Concurrent chemoradiotherapy for squamous cell carcinoma of the anus using a shrinking field radiotherapy technique without a boost.
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Chemoradiotherapy (CRT) is now widely accepted as the primary treatment modality for squamous cell cancer of the anus. While randomised trials have clearly shown CRT to be more effective than radiotherapy alone, there remains uncertainty over the optimal integration of chemotherapy and radiation. We describe a series of 50 patients treated by a site specialist gastrointestinal nonsurgical oncologist with CRT at a single UK centre. Chemotherapy comprised mitomycin C (MMC) (day 1) and 5-fluorouracil (5-FU) (days 1-4, and 29-32), concurrent with 50 Gy in 25 fractions radiation, using a two-phase shrinking field technique. A radiation boost was not planned. At a median follow-up of 48 months, 11 (22%) of the patients have failed locally, of which three have been surgically salvaged. Nine (18%) have died of anal cancer. These results are comparable with those from large randomised studies, and suggest that a two-phase shrinking field radiotherapy technique with no boost, concurrent with MMC/5-FU chemotherapy, is an effective regimen for this disease. The CRT regimen described here provides the basis for the 'control arm' of the current UK-randomised CRT trial in anal cancer (ACT2). (+info)
Expression of p16, Rb, and p53 proteins in squamous cell carcinomas of the anorectal region harboring human papillomavirus DNA.
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Human papillomavirus (HPV) has been implicated as an etiologic agent for the development of squamous cell carcinoma of the anorectal region. It has been shown that the HPV E6 and E7 oncoproteins are able to inactivate the tumor suppressor functions of p53 and Rb. In cervical and head and neck cancers, HPV infection is also associated with an overexpression of p16, a cyclin-dependent kinase inhibitor. The expression of these cell cycle regulators in squamous cell carcinomas of the anorectal region has not been well studied. In the current study, 29 cases of squamous cell carcinoma of the anorectal region were immunohistochemically examined for the expression of p16, Rb, and p53 proteins. Tumor cell DNA was also extracted from paraffin blocks and subjected to broad-spectrum HPV DNA testing and typing. The results show that the tumor cells exhibited a strong and diffuse nuclear stain (with some cytoplasmic positivity) for p16 in all 29 cases (100%). The adjacent nonneoplastic squamous epithelium or colonic mucosa, in contrast, was completely negative. Loss of Rb nuclear staining in tumor cells was observed in 20 cases (69%). The p53 protein was essentially undetectable, with only 6 cases containing <10% positive cells. HPV DNA was detected in every case (100%), with 25 cases (86%) harboring Type 16. In addition, almost identical results were obtained in 12 HPV-positive squamous cell carcinomas of the upper aerodigestive tract. This was in marked contrast to those of HPV-negative tumors, where positive p16 staining and loss of Rb expression were seen in only 2/21 (10%) and 1/21 (5%) cases, respectively. These observations indicate that overexpression of p16 and loss of Rb nuclear staining are commonly associated with high-risk HPV infection, which may serve as useful surrogate biomarkers for identifying squamous cell carcinomas harboring HPV DNA. (+info)
Randomised controlled trial and economic evaluation of podophyllotoxin solution, podophyllotoxin cream, and podophyllin in the treatment of genital warts.
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OBJECTIVES: To evaluate the efficacy and cost effectiveness of self applied podophyllotoxin 0.5% solution and podophyllotoxin 0.15% cream, compared to clinic applied 25% podophyllin in the treatment of genital warts over 4 weeks. METHODS: We conducted a randomised controlled trial in 358 immunocompetent men and women with genital warts of 3 months' duration or less. RESULTS: In the principal analysis both podophyllotoxin solution (OR 2.93, 95% CI 1.56 to 5.50) and podophyllotoxin cream (OR 1.97, 95% CI 1.04 to 3.70) were associated with significantly increased odds of remission of all warts compared to podophyllin. We performed two further analyses. When subjects defaulting from follow up were assumed to have been cured odds of remission of all warts were also significantly increased both for podophyllotoxin solution (OR 3.04, 95% CI 1.68 to 5.49) and for podophyllotoxin cream (OR 2.46, 95% CI 1.38 to 4.40). When subjects defaulting from follow up were assumed not to have been cured odds of remission of all warts were significantly increased for podophyllotoxin solution (OR 1.92, 95% CI 1.13 to 3.27), but not for podophyllotoxin cream (OR 1.17, 95% CI 0.69 to 2.00). Local side effects were seen in 24% of subjects, and recurrence of warts within 12 weeks of study entry in 43% of all initially cleared subjects, without statistically significant differences between the treatment groups. Direct, indirect, and total costs were similar across the three treatment groups. Podophyllotoxin solution was the most cost effective treatment, followed by podophyllotoxin cream, with podophyllin treatment being the least cost effective. CONCLUSIONS: Self treatment of anogenital warts with podophyllotoxin showed greater efficacy and cost effectiveness than clinic based treatment with podophyllin. (+info)
Squamous cell carcinoma of the anus: another sexually transmitted disease.
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During the past 30 years, there has been remarkable progress in our understanding of the pathogenesis of squamous cell carcinoma of the anus. It is now accepted that anal cancer is a sexually transmitted disease, which can be cured using a combination of chemo- and radiotherapy. The biology of anal cancer remains to be elucidated, as do the molecular mechanisms involved in resistance to chemoradiation. The contribution of HIV infection to tumour progression currently represents an area of intensive investigation. Finally, the growing numbers of AIDS patients who experience prolonged survival represent a population at risk. In the future, cytological screening of male homosexuals with an anal Papanicolaou test may help in identifying high-grade dysplasia and preventing anal cancer. (+info)
Human papillomavirus and HIV coinfection and the risk of neoplasias of the lower genital tract: a review of recent developments.
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One of the risk factors for human papillomavirus (HPV) infection and subsequent lower genital tract neoplasias and cancers is impaired cell-mediated immunity. HIV-positive women with severe immunosuppression are 5 times more likely than HIV-negative women to have lower genital tract neoplasias. A corresponding increase in the risk of invasive vulvar and anal cancers, but not of cervical cancer, has also been observed among HIV-positive women. Treatment failure and recurrence of neoplasia occur much more frequently among HIV-positive than among HIV-negative women. In this review, we discuss recent advances in the understanding of the relation between HIV and HPV coinfection and the development of lower genital tract neoplasias and cancers in women. In addition, we present strategies for monitoring and treating noninvasive and invasive neoplasias of the lower genital tract in HIV-positive women. (+info)
Synchronous squamous and glandular neoplasia of the anal canal.
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A 48 year old man presented with invasive adenocarcinoma in the wall of a non-healing anal fistula. The subsequent abdomino-perineal resection specimen showed residual invasive carcinoma coexisting with in situ carcinoma of anal glands as well as in situ squamous carcinoma of the anal canal. The epithelium of the anal canal had koilocytotic features. DNA hybridisation studies by the dot blot technique showed weak positivity for human papillomavirus (HPV) subtypes 16, 18. This case illustrates a number of important points--namely, anal fistulas, particularly non-healing fistulas should be biopsied to exclude malignancy; some adenocarcinomas of the anal arise in anal glands; the coexistence of glandular and squamous carcinoma with evidence of HPV infection is highly reminiscent of similar synchronous lesions of the uterine cervix and suggests that HPV may have an aetiological role in both squamous and glandular carcinomas of the anal canal. (+info)
Human papillomavirus infection and anal carcinoma. Retrospective analysis by in situ hybridization and the polymerase chain reaction.
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To examine the association of human papillomavirus (HPV) infection with anal squamous cell carcinoma, the authors applied the highly sensitive polymerase chain reaction (PCR) and in situ hybridization (ISH) techniques to detect HPV DNA in formalin-fixed, paraffin-embedded tissues from 18 patients. The presence of HPV types 16/18 in 3 (16.7%) of 18 patients with anal carcinoma was found, using a colorimetric ISH technique for HPV types 6, 11, 16, 18, 31, 35, and 51. Results from one of these three patients were also positive for HPV 31, 35, 51 by ISH techniques. When the same series was analyzed using the PCR and consensus primers to the L1 open reading frame of the HPV genomes, the frequency of positive patients rose to 14 (77.8%) of 18. PCR analysis of the 14 lesions containing HPV DNA, using type-specific primers and probes for HPV 6, 11, 16, 18, and 33, showed that 1 contained HPV 6, 1 contained HPV 11, 4 contained HPV 16, 1 contained HPV 18, 1 contained HPV 33, 5 contained HPV of unclassified type(s), and 1 contained a mixture of three HPV types. There was concordance between typing of cases that were positive by ISH and PCR methods. These data agree with the concept that HPV, in particular type 16, is implicated in the pathogenesis of anal cancer. (+info)