"A recent report that 93 percent of invasive cervical cancers worldwide contain human papillomavirus (HPV) may be an understatement," due to underdetection. On reanalysis of the specimens, HPV was found in most supposedly HPV-negative cases, and "the worldwide HPV prevalence in cervical carcinomas is 99.7 percent." (Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. JM Walboomers et al. J Pathol 1999 Sep;189(1):12-19).
Walboomers - J Pathol 1999 abstract / PubMedThe human papillomavirus type 16 E6 gene alone is sufficient to
induce carcinomas in transgenic animals. S Song, HC Pitot, PF Lambert.
J Virol 1999 Jul;73(7):5887-5893. "We generated K14E6 transgenic mice
in which the HPV16 E6 gene was expressed in the basal layer of
epithelia, using the hK14 promoter. Expression of E6 increased cell
proliferation and induced epidermal hyperplasia. Skin tumors developed
in adult K14E6 mice with an incidence of about 7% at 1 year of age. In
contrast to the tumors derived from K14E7 transgenic mice, which were
primarily benign, tumors derived from K14E6 transgenic mice were mostly
malignant, indicating that E6 alone not only is sufficient to induce
tumors but may contribute to the development of malignancy in animals."
"Inactivation of p53, however, may not be the only mechanism for
E6-induced carcinogenesis. The K14E6 mice that developed tumors also
displayed hyperplastic changes in the epidermis, a property that, as
discussed above, cannot be ascribed to E6's inactivation of p53. It is
likely that the hyperproliferation induced by E6 is important for its
carcinogenesis. Another activity that may contribute to E6-associated
carcinogenesis is its apparent inhibition of cellular differentiation.
Cancer cells usually lack the ability to terminally differentiate. In
this study, we found that the suprabasal compartment of the K14E6
transgenic epidermis stained for K14, indicating that E6 may also
perturb cellular differentiation; this perturbation was caused by
p53-independent activities of E6."
A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions. M Durst, L Gissmann, H Ikenberg, H Zur Hausen. Proceedings of the National Academy of Sciences 1983 Jun 15;80(12):3812-3815. 61.1% of cervical carcinomas carried an HPV DNA sequence which had little or no resemblance to those of known HPV types. It was designated HPV 16.
Durst / PNAS 1983 abstractRelationships between 80 human papillomavirus genotypes and
different grades of cervical intraepithelial neoplasia: association and
causality. T Matsukura, M Sugase. Virology 2001 Apr 25;283(1):139-147.
38 skin and 42 genital HPV types were sought in 386 biopsy samples.
"[S]ingle genital, but no skin's HPVs were identified with more than 10
copies per cell in 354 CIN (88 CIN I, 94 CIN II, and 172 CIN III). HPVs
40, 42, 43, 54, 62, or 71 was found in 10 CIN I, while HPVs 18, 30, 39,
51, 56, 59, 66, 68, 69, or 82 was found in 35 CIN I, 20 CIN II, or 8
CIN III. On the other hand, HPVs 16, 31, 33, 35, 52, 58, or 67 was
identified in 43 CIN I, 74 CIN II, or 164 CIN III. The results are
strongly indicative that most genital HPVs have potency to induce CIN
I; however, HPV 16 and its closely related types are able to
efficiently induce CIN III. We discuss the definition of causal HPV for
CIN with regard to viral prevalence and viral load."
Variation in the E2-binding domain of HPV 16 is associated with
high-grade squamous intraepithelial lesions of the cervix. A
Gainnoudis, M Duin, PJ Snijders, CS Herrington. Br J Cancer 2001
Apr;84(8):1058-1063. "[D]isruption of the regions of E2 analysed was
significantly more frequent in high-grade lesions, and there was a
significant association between the 3684C-A variant in the E2 DNA
binding domain and high-grade histology suggesting that this variant
may be important in progression to high-grade intraepithelial disease."
Asian-American variants of human papillomavirus 16 and risk for cervical cancer: a case-control study. J Berumen, RM Ordonez, E Lazcano, J Salmeron, SC Galvan, RA Estrada, E Yunes, A Garcia-Carranca, G Gonzalez-Lira, A Madrigal De- La Campa. J Natl Cancer Inst 2001 Sep 5;93(17):1325-1330; and: Aggressive HPV variant common among Mexican women with cervical cancer. Medscape - Reuters Health 2001 Sep 4.
Berumen - JNCI 2001 abstract / PubMedCpG Methylation of Human Papillomavirus Type 16 DNA in Cervical
Cancer Cell Lines and in Clinical Specimens: Genomic Hypomethylation
Correlates with Carcinogenic Progression. V Badal, LS Chuang, EH Tan, S
Badal, LL Villa, CM Wheeler, BF Li, HU Bernard. J Virol 2003
Jun;77(11):6227-6234. "In 81 patients from two different cohorts, the
LCR and the E6 gene of HPV-16 DNA were found to be hypermethylated in
52% of asymptomatic smears, 21.7% of precursor lesions, and 6.1% of
invasive carcinomas. This suggests that neoplastic transformation may
be suppressed by CpG methylation, while demethylation occurs as the
cause of or concomitant with neoplastic progression.... Two speculative
and opposing views might explain this observation. The cell may have an
antiviral defense that senses viral DNA as foreign and targets it for
transcriptional repression. Alternatively, DNA methylation may be yet
another example of the numerous strategies developed by HPVs that favor
a subclinical, long-term maintenance of the viral infection. Such a
model would be reminiscent of the life cycle of Epstein-Barr virus,
which includes DNA methylation-dependent silencing of a specific
promoter during one form of latency."
Human papillomavirus type 16 E6 and E7 genotypes in head-and-neck
carcinomas. M Hoffmann, C Lohrey, A Hunziker, T Kahn, E Schwarz. Oral
Oncol 2004 May;40(5):520-524. "Sequence analysis of the E6-E7 segments
revealed three different HPV16 E6-E7 genotypes: the HPV16 prototype (6
of 21 cases), the E6 variant T350G (8 of 21 cases), and the E6-E7
variant A131G/C712A (7 of 21 cases). The E6 variants T350G and A131G
have been associated with increased oncogenic potential in cervical
cancer patients depending on host genetic factors. Their high
prevalence in the HNSCC samples studied indicates that they may be
important also in HNSCC development."
Enhanced oncogenicity of Asian-American human papillomavirus 16 is
associated with impaired E2 repression of E6/E7 oncogene transcription.
RM Ordonez, AM Espinosa, DJ Sanchez-Gonzalez, J Armendariz-Borunda, J
Berumen. J Gen Virol 2004 Jun;85(Pt 6):1433-1444. "AA variants confer a
nine times higher risk than E variants for cervical cancer... The low
repression activity of E2 suggests that increased expression of E6/E7
oncogenes may occur much earlier in AA tumours. Therefore, the time
period between viral infection and the emergence of a frankly invasive
cancer may be decreased. This hypothesis could explain the association
of the AA-c variant with patients 11 years younger than those with E
variants (Berumen et al., 2001)."
Two distinct activities contribute to human papillomavirus 16 E6's
oncogenic potential. SJ Simonson, MJ Difilippantonio, PF Lambert.
Cancer Res 2005 Sep 15;65(18):8266-8273. "A very different finding was
made when we monitored carcinoma development, a measure of progression.
Here, we found that, compared with nontransgenic mice, a significantly
greater percentage of mice in both K14E6WT (P = 0.005) and K14E6146-151
(P = 0.002) groups developed carcinomas (Fig. 2B). This result
indicates that, although E6's interactions with PDZ domain proteins
correlate with E6's ability to act in the promotion stage of
carcinogenesis, these PDZ interactions are not required for E6's
progression activity in carcinogenesis. This is the first evidence
showing that the contribution of E6 to the multiple stages of
carcinogenesis can be mechanistically separated." "This provides the
first direct evidence that distinct activities of E6 contribute to
distinct stages in carcinogenesis. We suspect that this other property
is E6's inactivation of p53, as mice deficient for p53 specifically
show an enhanced rate and incidence of progression but no increase in
initiation or promotion."
Genome wide expression analysis in HPV16 cervical cancer:
Identification of altered metabolic pathways. C Perez-Plasencia, G
Vazquez-Ortiz, R Lopez-Romero, P Pina-Sanchez, J Moreno, M Salcedo.
Infectious Agents and Cancer 2007;2(16): in progress. "We found 2,067
genes significantly up or down-modulated (at least 2-fold) in tumor
clinical samples compared to normal tissues, representing ~ 3.7% of
analyzed genes. Cervical carcinoma was associated with an important
up-regulation of Wnt signaling pathway, which was validated by in situ
hybridization in clinical samples. Other up-regulated pathways were
those of calcium signaling and MAPK signaling, as well as cell
cycle-related genes. There was down-regulation of focal adhesion,
TGF-beta signaling, among other metabolic pathways."
Human papillomaviruses: Some genital-mucosal types. "Known to be a
human carcinogen. First listed in the Eleventh
Report on Carcinogens (2004)."
Mapping and analysis of HPV16 integration sites in a head and neck
cancer cell line. CC Ragin, SC Reshmi, SM Gollin. Int J Cancer 2004 Jul
10;110(5):701-709. "Disruption of the E2 gene sequence due to viral
integration results in upregulation of E6 and E7, which promote
tumorigenesis by abrogating p53 and pRb functions.... Sequential FISH
and spectral karyotyping identified integration sites on chromosomes 3,
6, 9q, 13q and t(1;8)(q;?). Restriction site-polymerase chain reaction
(RS-PCR) was performed to identify the viral-cellular junctions.
Sequence analyses confirmed integration sites at 9q31.1 and 6p21 and
revealed a novel junction at 16p12.3. Subsequent chromosome breakage
studies suggested that the observed viral-cellular integration sites
may have occurred within common fragile sites. Additional studies using
RT-PCR for E6--E7 viral transcripts showed oncoprotein expression from
episomal and integrated viral sequences. Our results suggest that viral
integration of HPV in SCCHN appears to occur nonrandomly through
targeting specific chromosomal sequences prone to breakage."
Mechanisms of human papillomavirus-induced oncogenesis. K Munger, A Baldwin, KM Edwards, H Hayakawa, CL Nguyen, M Owens, M Grace, KW Huh. Journal of Virology 2004 Nov;78(21):11451-11460. Minireview. The oncogenic E6 and E7 protein-expressing sequences of human papillomavirus are integrated into human genes, and continue to express their proteins; while the E2 protein-expressing sequence, which supresses transcription, is often lost or its expression is disturbed. The E6 proteins bind to and degrade the cell's p53 tumor suppressor protein, and prevent it from causing the death of damaged or mutated cells. HPV E6 proteins also have independent transforming abilities. The E7 protein inactivates the cell's pRb protein, which results in excessive cell proliferation. The E6 and E7 proteins also collaborate to induce telemerase activity which immortalizes the cell, and they cause centrosome abnormalities during cell division as well.
Munger / J Virology 2004 full articlePapillomavirus capsid mutation to escape dendritic cell-dependent innate immunity in cervical cancer. R Yang, CM Wheeler, X Chen, S Uematsu, K Takeda, S Akira, DV Pastrana, RP Viscidi, RBS Roden. J Virol 2005 Jun;79(11):6741-6750. Mutations occuring in high-grade CIN and cervical cancer evade recognition by the immune system.
Yang / J Virol 2005 abstractThe carcinogenicity of human papillomavirus types reflects viral
evolution. M Schiffman, R Herrero, R Desalle, A Hildesheim, S
Wacholder, AC Rodriguez, MC Bratti, ME Sherman, J Morales, D Guillen, M
Alfaro, M Hutchinson, TC Wright, D Solomon, Z Chen, J Schussler, PE
Castle, RD Burk. Virology 2005 Jun 20;337(1):76-84. Population-based
study of 10,000 women in Costa Rica. "HPV16 was uniquely likely both to
persist and to cause neoplastic progression when it persisted, making
it a remarkably powerful human carcinogen that merits separate clinical
consideration.... Other carcinogenic types, many related to HPV16, were
not particularly persistent but could cause neoplastic progression, at
lower rates than HPV16, if they did persist. Some low-risk types were
persistent but, nevertheless, virtually never caused CIN3. Therefore, carcinogenicity is not strictly
a function of persistence [emphasis added]. Separately, we noted
that the carcinogenic HPV types code for an E5 protein, whereas most
low-risk types either lack a definable homologous E5 ORF and/or a
translation start codon for E5."
Worldwide Genomic Diversity of the High-Risk Human Papillomavirus
Types 31, 35, 52, and 58, Four Close Relatives of Human Papillomavirus
Type 16. IE Calleja-Macias, LL Villa, JC Prado, M Kalantari, B Allan,
A-L Williamson, L-P Chung, RJ Collins, RE. Zuna, ST Dunn, T-Y Chu, HA
Cubie, K Cuschieri, M von Knebel-Doeberitz, CR Martins, GI Sanchez, FX
Bosch, N Munoz, H-U Bernard. Journal of Virology, 2005
Nov;79(21):13630-13640.
The Human DEK Proto-Oncogene Is a Senescence Inhibitor and an
Upregulated Target of High-Risk Human Papillomavirus E7. TM
Wise-Draper, HV Allen, MN Thobe, EE Jones, KB Habash, K Münger,
and SI Wells. J Virology, 2005 Nov;79(22): 14309-14317.
Development of a sensitive and specific assay combining multiplex
PCR and DNA microarray primer extension to detect high-risk mucosal
human papillomavirus types. T Gheit, S Landi, F Gemignani, PJ Snijders,
S Vaccarella, S Franceschi, F Canzian, M Tommasino. J Clin Microbiol
2006 Jun;44(6):2025-2031. "The importance of assays for the detection
and typing of human papillomaviruses (HPVs) in clinical and
epidemiological studies has been well demonstrated. Several accurate
methods for HPV detection and typing have been developed. However,
comparative studies showed that several assays have different
sensitivities for the detection of specific HPV types, particularly in
the case of multiple infections. Here, we describe a novel one-shot
method for the detection and typing of 19 mucosal high-risk (HR) HPV
types (types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59,
66, 68, 70, 73, and 82). This assay combines two different techniques:
multiplex PCR with HPV type-specific primers for amplification of viral
DNA and array primer extension (APEX) for typing. This novel method has
been validated with artificial mixtures of HPV DNAs and clinical
samples that were already analyzed for the presence of mucosal HPV
types by a different consensus PCR method, i.e., GP5+/GP6+. Our data
showed a very good agreement between the results from the multiplex
PCR/APEX assay and those from the GP5+/GP6+ PCR (overall rates of HPV
positivity, 63.0 and 60.9%, respectively). Whereas the GP5+/GP6+ PCR
was slightly more sensitive for the detection of HPV type 16 (HPV-16),
multiplex PCR-APEX found a higher number of infections with HPV-33,
HPV-53, and multiple HPV types."
Human papillomavirus causes an angiogenic switch in keratinocytes
which is sufficient to alter endothelial cell behavior. W Chen, F Li, L
Mead, H White, J Walker, DA Ingram, A Roman. Virology 2007 Oct
10;367(1):168-174. "Here we report that HPV-induced early changes in
the keratinocyte phenotype are sufficient to alter endothelial cell
behavior both in vitro and in vivo. Conditioned media from HPV16 E6E7
expressing HFKs as well as from human cervical keratinocytes containing
the intact HPV16 were able to stimulate proliferation and migration of
human microvascular endothelial cells. In addition, introduction of the
conditioned media into immunocompetent mice using a Matrigel plug model
resulted in a clear angiogenic response. These novel data support the
hypothesis that HPV proteins contribute not only to the uncontrolled
keratinocyte growth seen following HPV infection but also to the
angiogenic response needed for tumor formation."
Concerning attempts to implicate chemical carcinogens from cigarette smoke as cofactors with HPV: "Attempts to determine the importance of cofactors utilizing in vitro models with human cells and recombinant HPV have been frustrating. In general, there is a marked contrast between the effects of a carcinogen on rodent and human cells. Whereas a number of chemical and physical viral agents are effective in transforming normal rodent cells to the malignant state, they are for the most part ineffective when applied to human cells. The same can be said for cells that have been immortalized with HPV-16 or -18. The addition of diverse chemical carcinogens to HPV-16 immortalized cells has consistently failed to induce malignancy; however, evidence of effects has been obtained as reflected by new chromosomal rearrangements." (Immortalization of keratinocytes by human papillomaviruses. CD Woodworth, JA DiPaolo. In: DNA tumor viruses. Oncogenic mechanisms. G Barbanti-Brodano, M Bendinelli, H Friedman, eds. Plenum Press, 1995, Ch 6, pp 91-109.) Author DiPaolo has been a prominent anti-smoker, and both authors are from the National Cancer Institute. And, since enormous resources are always devoted to attempting to blame chemical carcinogens from tobacco, this failure would not be due to lack of trying. Animal cancers that were blamed on chemical carcinogens in bracken ferns have turned out to be caused by HPV, which resulted from immunosuppression from the toxicity of the substances.
ChemicalsEfficient repair of bulky anti-BPDE DNA adducts from non-transcribed
DNA strand requires functional p53 but not p21(waf1/cip1) and pRb. MA
Wani, MA El-Mahdy, FM Hamada, G Wani, Q Zhu, QE Wang, AA Wani. Mutat
Res 2002 Aug 29;505(1-2):13-25. "[T]he removal of anti-BPDE DNA adducts
from the genome overall and NTS by GGR was significantly reduced in
HPV-16E6 protein expressing cells as compared to that in normal and
HPV-16E7 protein expressing cells, indicating the role of p53 and not
pRb in nucleotide excision repair (NER).... the modulation of NER by
p53 may be independent of its function in the regulation of cell cycle
arrest upon chemically induced DNA damage."
Papillomavirus infection in association with feline cutaneous
squamous cell carcinoma in situ. SM LeClerc, EG Clark, DM Haines. Proc
Am Assoc Vet Derm/Am Coll Vet Derm 1997;13:125-126. As reported
in Sundberg 2000: "In a large case series of cutaneous squamous cell
carcinoma in situ in domestic cats, 30 of 63 biopsies were positive for
PV antigens. It is possible that negative tumors in this and other
studies were not associated with papillomavirus infections or that they
were intermittently productively infected, a phenomenon described for
other PV-induced lesions."
Feline papillomas and papillomaviruses. JP Sundberg, M Van Ranst, R
Montali, BL Homer, WH Miller, PH Rowland, DW Scott, JJ England, RW
Dunstan, I Mikaelian, AB Jenson. Vet Pathol 2000 Jan;37(1):1-10.
Review. "In general, the cat lesions, like their human counterparts
[epidermodysplasia verruciformis], are planar or flat warts with the
clinical appearance of plaques. In the human lesions, those associated
with HPV-5 and HPV-8 undergo conversion to malignancy in the presence
of ultraviolet light in approximately 30% of individuals. This may be
significant because cats frequently develop basal and squamous cell
carcinomas."
Clinical, histological and immunohistochemical study of feline viral
plaques and bowenoid in situ carcinomas. S Wilhelm, F Degorce-Rubiales,
D Godson, C Favrot. Vet Dermatol 2006 Dec;17(6):424-431. "Of the seven
cases in the FVP group, six were deemed positive by immunohistology as
were all 10 cats in the FVP + BISC group. On the other hand, only one
of the nine BISC cats was positive. The presence of both FVP and BISC
lesions in some cats and the high detection rate of PV antigens in the
FVP and FVP + BISC groups suggest that both conditions might have the
same viral cause and that some BISC may evolve from FVP. The low rate
of viral antigen detection in the BISC group indicates another cause or
a loss of viral replication during the cancerogenesis."
Detection of novel papillomaviruslike sequences in paraffin-embedded
specimens of invasive and in situ squamous cell carcinomas from cats. G
Nespeca, P Grest, WS Rosenkrantz, M Ackermann, C Favrot. Am J Vet Res
2006 Dec;67(12):2036-2041. "5 of 21 BISC specimens and 4 of 22 invasive
SCC specimens were positive for PV DNA on the basis of broad-range PCR
assay results. Sequence analysis revealed that only 1 specimen was
infected by a virus closely related to classic FePV. In the 8 other
specimens positive for PV DNA, DNA of unknown PVs was uncovered.
CONCLUSIONS AND CLINICAL RELEVANCE: Bowenoid in situ SCC and invasive
SCC of cats may be associated with PVs of genetic diversity."
Detection of papillomaviral sequences in feline Bowenoid in situ
carcinoma using consensus primers. JS Munday, M Kiupel, AF French, L
Howe, RA Squires. Vet Dermatol 2007 Aug;18(4):241-245. Papillomaviral
DNA was amplified from 11 of 18 formalin-fixed samples of BISC, but no
controls. "Six amplicons were sequenced; one was homologous with a
papillomavirus from a human patient with multiple cutaneous squamous
cell carcinomas and the other five showed weak homology to human
papillomavirus type 17. These five sequences were > 96% homologous
over a 235 bp sequence, indicating the presence in all five BISCs of
one papillomavirus type distinct from any previously sequenced and more
closely related to human than animal papillomaviruses. The results
confirm an association between BISC and papillomaviruses, and as all
six papillomavirus sequences identified are closely related to human
papillomaviruses, it is possible that the virus is transmitted from
humans to cats or vice versa."
Bovine papillomavirus E5 oncoprotein binds to the activated form of
the platelet-derived growth factor beta receptor in naturally occurring
bovine urinary bladder tumours. G Borzacchiello, V Russo, F Gentile, F
Roperto, A Venuti, L Nitsch, MS Campo, S Roperto. Oncogene 2006 Feb
23;25(8):1251-1260. "We have shown that BPV-2 DNA is present in the
majority of naturally occurring urinary bladder tumours of cattle and
that E5 is expressed in the cancer cells. Here we show that the
interaction between the platelet-derived growth factor (PDGF) beta
receptor and BPV E5, described in vitro in cultured cells, takes place
in vivo in bovine urinary bladder cancers. In these cancers, E5 and
PDGF beta receptor colocalize, as shown by confocal microscopy, and
physically interact, as shown by coimmunoprecipitation. Furthermore,
the PDGF beta receptor associated with E5 is highly phosphorylated,
suggesting the functional activation of the receptor upon E5
interaction. Our results demonstrate, for the first time, that E5-PDGF
beta receptor interaction occurs during the natural history of bovine
urinary bladder tumours, suggesting an important role for E5 in
carcinogenesis."
Epithelial neoplasms of the skin, the cutaneous mucosa and the transitional epithelium in dogs: an immunolocalization study for papillomavirus antigen. K Schwegler, JH Walter, R Rudolph. Zentralbl Veterinarmed A 1997 Apr;44(2):115-123. 44.2% of 95 papillomas and 27% of 100 diagnosed squamous cell carcinomas reacted with antiserum. "Papillomavirus antigen was detectable in 54.2% of all oral and ocular papillomas and in 37.0% of all cutaneous papillomas. The majority of the squamous cell carcinomas with detectable papillomavirus antigen were considered positive but not without restrictions. The average age of dogs with viral oral and ocular papillomas was 2.3 years, with viral cutaneous papillomas it was 3.2 years. The average age of dogs with virus-positive squamous cell carcinomas was nearly 11 years. Papillomavirus-like particles were demonstrated by means of transmission electron microscopy in three positive oral papillomas, in the positive squamous cell carcinomas virion detection failed."
Schwegler - Zentralbl Veterinarmed A 1997 abstract / PubMedDetection of canine oral papillomavirus-DNA in canine oral squamous
cell carcinomas and p53 overexpressing skin papillomas of the dog using
the polymerase chain reaction and non-radioactive in situ
hybridization. JP Teifke, CV Löhr, H Shirasawa. Vet Microbiol 1998
Feb 28;60(2-4):119-30. 29 oral and 25 non-oral squamous cell carcinomas
of dogs. Fragments of the E6, E7 and L1 gene were amplified by
polymerase chain reaction (PCR) from five of eight oral and from five
of eight cutaneous papillomas as well as from three oral squamous cell
carcinomas. "In three squamous cell carcinomas COPV-DNA was located in
nests of the epithelial tumor cells surrounding 'horn pearls' or
disseminated in the carcinoma tissue. These observations support the
view that COPV may also induce non-oral papillomas in the dog and
confirm the opinion that a progression of viral papillomas into
carcinomas in dogs may occur."
Detection of novel papillomaviruses in canine mucosal, cutaneous and
in situ squamous cell carcinomas. N Zaugg, G Nespeca, B Hauser, M
Ackermann, C Favrot. Vet Dermatol 2005 Oct;16(5):290-298. "While
approximately 100 human PVs are known, only one single canine oral PV
(COPV) has been identified and studied extensively. Therefore, we
applied a narrow-range polymerase chain reaction (PCR) suitable for the
detection of classical canine and feline PVs, as well as a broad-range
PCR, which has been used for the detection of various novel PVs in
humans, in order to analyse 42 paraffin-embedded samples, representing
three different forms of canine SCCs. Ten samples of skin tissues with
various non-neoplastic conditions served as controls. While none of the
negative controls reacted positively, PV DNA was discovered in 21% of
the tested SCC samples. Interestingly, the classical COPV was amplified
from only one sample, while the other positive cases were associated
with a variety of thus far unknown PVs. This study suggests that a
fraction of canine SCC is infected with PVs and that a genetic variety
of canine PVs exists."
An epidermotropic canine papillomavirus with malignant potential
contains an E5 gene and establishes a unique genus. H Yuan, S Ghim, J
Newsome, T Apolinario, V Olcese, M Martin, H Delius, P Felsburg, B
Jenson, R Schlegel. Virology 2007 Mar 1;359(1):28-36. "CfPV-2
establishes a new PV genus, with its closest phylogenetic relatives
being amongst the Xi and Gamma genuses. CfPV-2 also has unique
biological features; it induces papillomas on footpads and interdigital
regions which, if infection is persistent, can progress to highly
metastatic squamous cell carcinoma. CfPV-2 does not induce oral
papillomas in immunocompetent animals and antibodies generated against
COPV and CfPV-2 are type-specific."
Presence of a novel hamster oral papillomavirus in dysplastic
lesions of hamster lingual mucosa induced by application of
dimethylbenzanthracene and excisional wounding: molecular cloning and
complete nucleotide sequence. T Iwasaki, H Maeda, Y Kameyama, M
Moriyama, S Kanai, T Kurata. J Gen Virol 1997 May;78 ( Pt 5):1087-1093.
"All dysplastic lesions induced by this combination of DMBA application
and excisional wounding contained viral DNA. Although Southern blot
hybridization analysis
could not detect the HOPV genome, PCR analysis demonstrated the latent
HOPV genome in the tongue and skin of an untreated hamster. These
results suggest that latently present HOPV genome is reactivated by the
DMBA/wounding procedures." Viral particles resembling papillomavirus
were detected in the nuclei as far back as 1986.
DNA vaccine against hamster oral papillomavirus-associated oral
cancer. H Maeda, K Kubo, Y Sugita, Y Miyamoto, S Komatsu, S Takeuchi, T
Umebayashi, S Morikawa, K Kawanishi, Y Kameyama. J Int Med Res 2005
Nov-Dec;33(6):647-653. "Previously we developed a carcinogenesis model
involving the combination of 9,10-dimethyl-1,2-benzanthracene (DMBA)
application with physical wounding of hamster lingual mucosa. The
presence of a novel hamster oral papillomavirus (HOPV) was demonstrated
and its genome sequenced.... All control hamsters developed lingual
carcinoma, whereas 12 of the L1-vaccinated hamsters showed no lesions."
There were 20 vaccinated and 20 control animals.
Cloning and characterization of a papillomavirus associated with
papillomas and carcinomas in the European harvest mouse (Micromys
minutus). MK O'Banion, ME Reichmann, JP Sundberg. J Virol 1988
Jan;62(1):226-233. "All 17 tumors examined contained large amounts of
viral DNA in a supercoiled, unintegrated form as revealed by Southern
blot hybridization. Furthermore, many extracts (25 of 35) from normal
organs and skin of individuals with lesions elsewhere on their bodies
contained viral DNA." "[H]igh copy numbers and the presence of viral
antigens indicate that productive infection was occurring in many of
these tissues. Although insufficient sample numbers preclude a final
conclusion, the observations that no viral antigens were detected in
two sebaceous carcinomas and that the viral DNA copy number was low
(100 copies) in the one carcinoma examined
suggest that productive infection was not occurring in these lesions."
Viral DNAs were also detected in many apparently normal tissues from
affected individuals.
The Mastomys natalensis papillomavirus: nucleotide sequence, genome
organization, and phylogenetic relationship of a rodent papillomavirus
involved in tumorigenesis of cutaneous epithelia. CH Tan, R Tachezy, M
Van Ranst, SY Chan, HU Bernard, RD Burk. Virology 1994
Feb;198(2):534-541. "Mastomys natalensis is a rodent of African origin
afflicted with a very high incidence of skin tumors (keratoacanthomas
and squamous carcinomas), which are associated with a papillomavirus,
M. natalensis papillomavirus (MnPV)." It is similar to several HPV
types that are associated with epidermodysplasia verruciformis.
A transactivator function of cottontail rabbit papillomavirus e2 is
essential for tumor induction in rabbits. S Jeckel, E Huber, F
Stubenrauch, T Iftner. J Virol 2002 Nov;76(22):11209-11215. "In
contrast to the productive virus infection observed in the cottontail
rabbit, which is the natural host, infection of New Zealand White
rabbits with CRPV causes an abortive infection. As many as 80% of the
initially benign epithelial tumors progress to carcinomas within the
next 6 to 14 months, and these finally metastasize without the need for
cofactors."
cast 01-12-08