Molecular and serological studies of human papillomavirus among patients with anal epidermoid carcinoma

Heino, Pirkko; Goldman, Sven; Lagerstedt, U.; Dillner, Joakim

doi:10.1002/ijc.2910530306

Cited by 30 publications

(10 citation statements)

References 21 publications

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“…The E2 encodes two proteins which inhibit and activate the early region, respectively. A hallmark of HPV-associated cervical carcinoma is the loss of this E2 protein expression 6. In addition to modulating viral gene expression, the E2 proteins are associated with the viral helicase E1.…”

Section: Introductionmentioning

confidence: 99%

Human Papillomavirus Type 16 E5 Protein as a Therapeutic Target

Kim

Yang

2006

Yonsei Med J

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Cervical cancer is a progressive disease with an onset of one to two decades on average. During the productive replication stage, the Human papillomavirus (HPV) genome is maintained episomally in the infected cervical epithelium and early gene products, including E5, are expressed. Therefore, E5 has a potential to contribute to the HPV-associated carcinogenic process. In invasive malignancies, the HPV genomes are commonly integrated into the host genome, and E6 and E7 genes remain intact. However, the E5 is lost or, if present, under-expressed as compared with the E6 and E7 proteins. This suggests that E5 may play a critical role in the genesis of cervical cancer but less of a role in its persistence or progression. In the initiation of neoplasia and the premalignant stage, there are fewer malignant cells than in the invasive malignancies. Moreover, cells in the invasive malignant stage are found to have a very low level of MHC class I and II, which could hamper the presentation of the antigen and lead to a decreased immune response. Since the E5 protein is likely to play a role during the early tumorigenesis stage, a therapeutic vaccine to target and eliminate the E5-expressing cells may be a good strategy to prevent premalignant lesions from progressing toward invasive cervical cancers. This paper provides an overview of HPV-induced cervical carcinogenesis and strategies for designing prophylactic and therapeutic vaccines to prevent and cure the cervical cancer. In particular, focus will be on the rationale of targeting the E5 protein to develop therapeutic vaccines.

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Section: Introductionmentioning

confidence: 99%

Human Papillomavirus Type 16 E5 Protein as a Therapeutic Target

Kim

Yang

2006

Yonsei Med J

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“…Patients with HPV DNA in their anal tumours have been reported to be about 10 years younger than those with HPV DNA-negative anal cancers (Heino et al, 1993). In this study, the mean age of the cases being seropositive for any HPV was 54 years, whereas the mean age of the seronegative cases was 53 years.…”

Section: Discussionmentioning

confidence: 56%

Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study

et al. 2002

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Human papillomavirus has emerged as the leading infectious cause of cervical and other anogenital cancers. We have studied the relation between human papillomavirus infection and the subsequent risk of anal and perianal skin cancer. A case -cohort study within two large Nordic serum banks to which about 760 000 individuals had donated serum samples was performed. Subjects who developed anal and perianal skin cancer during follow up (median time of 10 years) were identified by registry linkage with the nationwide cancer registries in Finland and Norway. Twenty-eight cases and 1500 controls were analysed for the presence of IgG antibodies to HPV 16, 18, 33 or 73, and odds ratios of developing anal and perianal skin cancer were calculated. There was an increased risk of developing anal and perianal skin cancer among subjects seropositive for HPV 16 (OR=3.0; 95%CI=1.1 -8.2) and HPV 18 (OR=4.4; 95%CI=1.1 -17). The highest risks were seen for HPV 16 seropositive patients above the age of 45 years at serum sampling and for patients with a lag time of less than 10 years. This study provides prospective epidemiological evidence of an association between infection with HPV 16 and 18 and anal and perianal skin cancer. Anal epidermoid carcinoma is a rare tumour, but its incidence has increased over the past 30 years (Goldman et al, 1989;Frisch et al, 1993;Melbye et al, 1994). Sexual behaviour and smoking are risk factors (Daling et al, 1992;Frisch et al, 1997). A high proportion of anal tumours are associated with human papillomavirus (HPV) infection (Melbye and Frisch, 1998). HPV 16 DNA has been reported in up to 93% of invasive squamous anal tumours and 69% of anal carcinoma in situ (Tilston, 1997).Most epidemiological studies on HPV infection and anal cancer have been case -series and case -control studies using samples taken after the cancer has been diagnosed. Such studies may be subject to differential misclassification related to the presence of the disease, and provide no information on the temporal order of events. Prospective studies are generally considered crucial for causality inference. As primary prevention of HPV infection by vaccination is being evaluated, it is important to establish which cancers are likely to be amenable to prevention. Prospective seroepidemiological studies have linked HPV to vulvar, vaginal and to a subset of head and neck cancers (Bjørge et al, 1997a;Mork et al, 2001).HPV serology, using capsids of HPV 16, 18 and 33, has been validated as a type-restricted marker of past or present HPV infection (Dillner, 1999). A serologic association of HPV 16 with incident anal cancer has been shown (Heino et al, 1995). In a study of the role of HPV in non-cervical anogenital cancers, we found that HPV 16 seropositivity conferred an increased risk for noncervical anogenital cancers, but not for anal cancer (Bjørge et al, 1997a). This was in spite of the fact that the proportion of anal cancer cases (25%) being HPV 16 seropositive was higher than for other non-cervical anogenital cancers (24%). This...

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“…Analogous differences among age at onset, histopathology, sexual behavioral associations, and biological behavior are emerging for HPV-positive and -negative penile, 32–42 anal, 43–45 and vaginal squamous cell carcinomas. 46,47 It is important to note, however, that the clinicopathological patterns observed for HPV-associated and unassociated cancers noted above are not absolute; 2 etiologically distinct cancers may, nevertheless, present as phenotypically identical tumors.…”

Section: Commentarymentioning

confidence: 99%

HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women

Gillison

Chaturvedi

Lowy

2008

Cancer

447

330

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Human papillomavirus (HPV) is a necessary cause of cervical cancer. In addition, on the basis of the fulfillment of a combination of viral as well as epidemiological criteria, it is currently accepted that a proportion of anal, oropharyngeal, vulvar, and vaginal cancers among women and anal, oropharyngeal, and penile cancers among men are etiologically related to HPV. At these noncervical sites with etiologic heterogeneity, HPV-associated cancers represent a distinct clinicopathological entity, which is generally characterized by a younger age at onset, basaloid or warty histopathology, association with sexual behavior, and better prognosis, when compared with their HPV-negative counterparts. Currently available estimates indicate that the number of HPV-associated noncervical cancers diagnosed annually in the US roughly approximates the number of cervical cancers, with an equal number of noncervical cancers among men and women. Furthermore, whereas the incidence of cervical cancers has been decreasing over time, the incidence of anal and oropharyngeal cancers, for which there are no effective or widely used screening programs, has been increasing in the US. The efficacy of HPV vaccines in preventing infection at sites other than the cervix, vagina, and vulva should, therefore, be assessed (eg, oral and anal). Given that a substantial proportion of cervical cancers (approximately 70%) and an even greater proportion of HPV-associated noncervical cancers (approximately 86% to 95%) are caused by HPV16 and 18 (HPV types that are targeted by the currently available vaccines), current HPV vaccines may hold great promise (provided equivalent efficacy at all relevant anatomic sites) in reducing the burden of HPV-associated noncervical cancers, in addition to cervical cancers.

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Molecular and serological studies of human papillomavirus among patients with anal epidermoid carcinoma

Cited by 30 publications

References 21 publications

Human Papillomavirus Type 16 E5 Protein as a Therapeutic Target

Human Papillomavirus Type 16 E5 Protein as a Therapeutic Target

Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study

HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women

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