HPV Sexually Transmitted Disease - Genital Cancer Treatment

Georgala S, Katoulis AC, Georgala C, Bozi E, Mortakis A. National and Kapodistrian University of Athens, Department of Dermatology and Venereology, "A Sygros" Hospital, Athens, Greece. eykat@panafonet.gr

BACKGROUND: Conventional therapies for human papillomavirus (HPV) infection are often associated with unsatisfactory response rates and high recurrence rates. The use of a systemic agent may more effectively control the virus. OBJECTIVES: To investigate the efficacy and safety of low dose oral isotretinoin in recalcitrant condylomata acuminata (RCA) of the cervix. METHODS: Double blind placebo controlled clinical trial. 60 women, aged 21-43 years, with RCA of the cervix, refractory to at least one conventional therapy, were randomly assigned to receive either isotretinoin, 0.5 mg/kg daily for 12 weeks (group 1), or placebo (group 2). RESULTS: Of the 28 evaluable group 1 patients, nine (32.1%) responded to the treatment completely, 11 (39.2%) responded partially, and eight (28.5%) did not respond. Of the 25 group 2 patients, no one responded to the treatment completely, two (8%) responded partially, and 23 (92%) did not respond. The therapeutic difference between patients receiving active and placebo therapy was statistically significant (chi(2) = 19.35, p<0.001). Only one (11.1%) of the complete responders experienced recurrence during the 12 month follow up. Side effects were generally mild and resolved upon completion of therapy. CONCLUSIONS: Compared to placebo, low dose oral isotretinoin showed considerable efficacy with insignificant and reversible side effects and a low recurrence rate. Isotretinoin may represent an efficacious and safe alternative systemic form of therapy for RCA of the cervix.

Publication Types:
• Clinical Trial
• Randomized Controlled Trial

Stewart D, Kazemi S, Li S, Massimi P, Banks L, Koromilas AE, Matlashewski G. Institute of Parasitology, MacDonald Campus, McGill University, Montreal, Canada, H9X 3V9.

Human papillomaviruses (HPVs) are aetiological agents for genital warts and cervical cancer, the different pathologies of which are dependent on the type of HPV infection. Oncogenic HPV types associated with cancer are carcinogens by virtue of their oncogene products, which target key regulators of cell proliferation and apoptosis. The viral E6 protein from oncogenic HPV types plays a central role in carcinogenesis by exploiting the cellular proteasome degradation pathway in order to mediate the degradation of cellular proteins, most notably the prototype tumour suppressor protein p53. Much less is known about the cellular targets of E6 from the non-oncogenic HPV types associated with genital warts. It is also unclear what factors influence the level and stability of the viral E6 proteins in cells. This report demonstrates that both oncogenic and non-oncogenic HPV E6 proteins (from types 18 and 11, respectively) are ubiquitinated and targeted for degradation by the 26S proteasome. E6 domains required for the induction of p53 or DLG degradation, or E6AP binding, are not involved in proteasome-mediated degradation of HPV-18 E6. These results provide insight into the cellular modulation of E6 protein levels from both high-risk and low-risk HPV types.

J Gen Virol. 2004 Jun;85(Pt 6):1419-26.

Ubiquitination and proteasome degradation of the E6 proteins of human papillomavirus types 11 and 18.

Stewart D, Kazemi S, Li S, Massimi P, Banks L, Koromilas AE, Matlashewski G. Institute of Parasitology, MacDonald Campus, McGill University, Montreal, Canada, H9X 3V9.

Human papillomaviruses (HPVs) are aetiological agents for genital warts and cervical cancer, the different pathologies of which are dependent on the type of HPV infection. Oncogenic HPV types associated with cancer are carcinogens by virtue of their oncogene products, which target key regulators of cell proliferation and apoptosis. The viral E6 protein from oncogenic HPV types plays a central role in carcinogenesis by exploiting the cellular proteasome degradation pathway in order to mediate the degradation of cellular proteins, most notably the prototype tumour suppressor protein p53. Much less is known about the cellular targets of E6 from the non-oncogenic HPV types associated with genital warts. It is also unclear what factors influence the level and stability of the viral E6 proteins in cells. This report demonstrates that both oncogenic and non-oncogenic HPV E6 proteins (from types 18 and 11, respectively) are ubiquitinated and targeted for degradation by the 26S proteasome. E6 domains required for the induction of p53 or DLG degradation, or E6AP binding, are not involved in proteasome-mediated degradation of HPV-18 E6. These results provide insight into the cellular modulation of E6 protein levels from both high-risk and low-risk HPV types.

Histopathology. 2004 Mar;44(3):216-21.

Condyloma acuminatum and condyloma-like lesions of the oral cavity: a study of 11 cases with an intraductal component.

Henley JD, Summerlin DJ, Tomich CE. Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. jhenley@iupui.edu

AIMS: We studied the clinicopathological features of 11 condyloma and condyloma-like lesions of the oral cavity with an unusual mixed pattern of exophytic and intraductal growth. The latter manifest as involvement of minor salivary gland ducts by the proliferative squamous lesions. This pattern of ductal involvement has not been previously described in oral condyloma. METHODS AND RESULTS: The clinical history was available for nine patients ranging in age from 17 to 73 years. Two were female and seven male. The buccal mucosa (five cases) was the most common site of occurrence, followed by the floor of mouth (two cases), lingual frenum (two cases), and hard palate (one case). All lesions exhibited exophytic and intraductal growth. The latter manifested itself as extension of the lesions into the excretory ducts of minor salivary glands. Underlying minor salivary glands, present in many of the excisional biopsy specimens, typically showed changes of obstructive atrophy. The exophytic components of all cases exhibited some degree of parakeratosis, and cryptic invaginations of parakeratin were typically present. Koilocytes were present in seven lesions and were equivocal in four. Mucous cells were present in the intraductal component of all cases and the intraductal component was never keratinized, but often papillary. A mild stromal-based, lymphocytic host response was present in three. A variably prominent neutrophilic infiltrate was present in the exophytic component of eight. Dysplasia was not present in any case. Five of 11 cases were positive with anti-human papillomavirus (HPV) and two of 11 cases were positive for in-situ hybridization probes directed against HPV 6/11. All cases were negative for HPV 16/18 and 13/33/35. CONCLUSIONS: Oral condyloma acuminatum may involve the excretory ducts of minor salivary glands. The diagnosis of oral condyloma acuminatum is difficult, as these lesions share considerable histological overlap with squamous papilloma. Finally, the relationship between these two lesions is incompletely understood.

Cancer. 2004 Jan 15;100(2):308-14.

Comment in:

News media coverage of human papillomavirus.

Anhang R, Stryker JE, Wright TC Jr, Goldie SJ. Harvard Center for Risk Analysis, Harvard School of Public Health, 718 Huntington Avenue, Suite 2, Boston, MA 02115-5924, USA.

BACKGROUND: Now that human papillomavirus (HPV) DNA testing is being incorporated into cervical cancer screening programs, salient and accurate media information about HPV will be crucial to inform women's screening choices and to manage psychosocial responses to HPV DNA test results. METHODS: The authors conducted a content analysis of 111 news stories about HPV from the 10 most circulated newspapers and from 3 major television networks for the period from January 1995 through July 2002. Stories were assessed for predominant theme (STD, cancer, or new tests); information about symptoms, transmission, prevention, and cancer-causing properties of HPV; screening test descriptions; and recommended screening guidelines. RESULTS: Thirty-six percent of stories primarily were about new tests for HPV or cervical cancer, 30% of stories focused on cervical cancer or its link to HPV, and 27% of stories emphasized sexually transmitted diseases (STDs) or genital warts. Seventy-nine percent of stories mentioned that HPV is an STD, and 50% of stories reported that HPV is very common. Twenty-six percent of stories reported that most women with HPV will not develop cervical carcinoma. Of 81 stories that mentioned a screening test for HPV or cervical carcinoma, 38% reported the sensitivity of the test; 30% mentioned wrong, uncertain, or unnecessary test results; and 25% mentioned consequences of such results. CONCLUSIONS: Media coverage of HPV could better fulfill women's educational needs by including information about low-risk and high-risk types of HPV and their differing links to cervical cancer; describing HPV prevention, transmission, and symptoms; explaining the benefits and consequences of HPV testing; and outlining the latest screening guidelines in every story. Copyright 2003 American Cancer Society.

Clin Exp Dermatol. 2003 Nov;28 Suppl 1:51-4.

Extensive condyloma acuminata treated with imiquimod 5% cream: a case report.

Cox JT. Department of Student Health Service, University of California at Santa Barbara, CA 93106, USA. cox-t@sa.ucsb.edu

Genital warts are one of the most common sexually transmitted infections, and are caused by human papillomavirus (HPV) types 6 and 11. Standard treatments for genital warts include cryotherapy, laser therapy, trichloroacetic acid and podophyllotoxin. We report the case of a 21-year-old female with extensive genital warts. A patient-applied, non-destructive therapy was considered to be the most appropriate treatment in this case, due to the extent of the disease and the resulting psychological distress experienced by the patient. She applied imiquimod 5% cream three times per week for a period of 5 weeks, which resulted in complete clearance of all the warts. Minor inflammatory changes were observed during treatment; however, no significant pain was by reported the patient. No recurrences were reported during 2 years of follow-up.

Publication Types:
• Case Reports

HPV Sexually Transmitted Disease - Genital Cancer Treatment Links

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