Pathology Of Genital Warts
HPVs are non-enveloped, double-stranded DNA viruses. The HPV genome encodes 6 early-open reading frames (E1, E2, E4, E5, E6, E7) and 2 late-open reading frames (L1, L2). Differences in L1 define HPV subtypes. The E genes encode proteins regulating function, and the L genes encode for viral capsid proteins.
Malignant tumors develop after long latency periods during which additional cellular modifications occur within the infected cell. The early region of these HPV types encodes two oncoproteins, E6 and E7, which associate with and neutralize the cellular tumor suppressors p53 and retinoblastoma (pRb), respectively. The virus initially infects the basal cell layer, and its life cycle is linked to the progressive differentiation of epithelial cells.
More than 120 distinct HPV subtypes have been identified. Of the 120 subtypes of HPV, 30 infect genital epithelium. Establishing the subtype of HPV helps to determine the likelihood of malignant degeneration but has no bearing on the diagnosis or treatment of genital warts. These subtypes are divided into 3 categories based on their likelihood of inducing dyplasia and carcinoma.
HPV types 6 and 11 are considered to be low risk and are the most common cause of genital warts. HPV types 31, 33, 45, 51, 52, 56, 58, and 59 are referred to be intermediate risk because they are common causes of squamous intraepithelial neoplasia but less common causes of squamous cell carcinoma. HPV types 16 and 18 are strongly associated with cervical dysplasia and anogenital cancers. Patients who have visible genital warts can be infected simultaneously with multiple HPV types.
Genetic mechanisms define the basis for HPV risk category. The E6 and E7 proteins of the low-risk types, HPV 6 and HPV 11, replicate as an episome and rarely incorporate their genetic material into the host DNA, although these proteins have been occasionally demonstrated in cancer cells. Intermediate and high risk HPV DNA intercalates itself into human DNA. Their E6 and E7 genes can produce oncoproteins that alter cell growth regulation. E6 oncoprotein inactivates p53, the tumor suppressor gene. The oncoprotein produced by E7 inactivates pRb.
The immune system plays a central role in regression of genital HPV disease via both cellular and humoral immunity. Spontaneously regressing genital warts show significant epidermal and dermal influx of CD4-activated memory lymphocytes compared to nonregressing lesions. Cellular immunity appears to be the prime means of repelling HPV infection.
The association of serum antibodies to HPV proteins with HPV-related diseases is well documented, but what role these antibodies play is uncertain because their presence does not correlate with wart clearance. Evidence suggests that T cells in male and the female genital epithelium secrete protective antibodies against many HPV infections, the significance of this is unclear.
Genital warts are almost spread by sexual contact but vertical transmission and autoinoculation do occur rarely. Approximately 70 percent of individuals who have sexual contact with an infected partner develop genital warts. The incubation period of HPV varies from 3 weeks to 8 months, with a mean of 2-3 months after initial contact.
The rate of subclinical infection is as high as 40 percent when measured by polymerase chain reaction DNA analysis on genital skin. After the initial clinical manifestation, warts may increase in number and size, or may regress spontaneously (as many as 30 % over 4 months). The rate of long-term regression is unknown.
Even with therapy, recurrence occurs within 3 months in 25-67 percent of cases. Recurrences are often at sites of previous genital warts, attributed to long-lived cells at the site of previous clearance that then reactivate. Infection with high-risk types of HPV and older age patients are risk factors for persistence.
Traditional theories postulated that once a person is infected, HPV remained in the body for a lifetime. However, new studies using sensitive DNA techniques have shown that an HPV cure (with the virus suppressed to levels below what PCR tests can measure) is possible through immunological response.
These studies further concluded that among other genital warts cures, HPVCurative best extracts "inhibited skin papillomas (HPV) and decreased the conversion of papillomas to carcinomas" which resulted in "significant apoptosis (disintegration) of HPV cells in DNA tests" without damaging surrounding healthy tissue.
HPVCurative contains stringently certified organic antiviral plant extracts, which have the ability to destroy the genital wart virus (HPV). The extracts are harvested and distilled by hand for medicinal use -- they are pure and complete. This is essential when creating HPV cures, and it is of critical importance when applying anything to the genitals. To learn more, please go to http://www.forcesofnatureusa.com.
Malignant tumors develop after long latency periods during which additional cellular modifications occur within the infected cell. The early region of these HPV types encodes two oncoproteins, E6 and E7, which associate with and neutralize the cellular tumor suppressors p53 and retinoblastoma (pRb), respectively. The virus initially infects the basal cell layer, and its life cycle is linked to the progressive differentiation of epithelial cells.
More than 120 distinct HPV subtypes have been identified. Of the 120 subtypes of HPV, 30 infect genital epithelium. Establishing the subtype of HPV helps to determine the likelihood of malignant degeneration but has no bearing on the diagnosis or treatment of genital warts. These subtypes are divided into 3 categories based on their likelihood of inducing dyplasia and carcinoma.
HPV types 6 and 11 are considered to be low risk and are the most common cause of genital warts. HPV types 31, 33, 45, 51, 52, 56, 58, and 59 are referred to be intermediate risk because they are common causes of squamous intraepithelial neoplasia but less common causes of squamous cell carcinoma. HPV types 16 and 18 are strongly associated with cervical dysplasia and anogenital cancers. Patients who have visible genital warts can be infected simultaneously with multiple HPV types.
Genetic mechanisms define the basis for HPV risk category. The E6 and E7 proteins of the low-risk types, HPV 6 and HPV 11, replicate as an episome and rarely incorporate their genetic material into the host DNA, although these proteins have been occasionally demonstrated in cancer cells. Intermediate and high risk HPV DNA intercalates itself into human DNA. Their E6 and E7 genes can produce oncoproteins that alter cell growth regulation. E6 oncoprotein inactivates p53, the tumor suppressor gene. The oncoprotein produced by E7 inactivates pRb.
The immune system plays a central role in regression of genital HPV disease via both cellular and humoral immunity. Spontaneously regressing genital warts show significant epidermal and dermal influx of CD4-activated memory lymphocytes compared to nonregressing lesions. Cellular immunity appears to be the prime means of repelling HPV infection.
The association of serum antibodies to HPV proteins with HPV-related diseases is well documented, but what role these antibodies play is uncertain because their presence does not correlate with wart clearance. Evidence suggests that T cells in male and the female genital epithelium secrete protective antibodies against many HPV infections, the significance of this is unclear.
Genital warts are almost spread by sexual contact but vertical transmission and autoinoculation do occur rarely. Approximately 70 percent of individuals who have sexual contact with an infected partner develop genital warts. The incubation period of HPV varies from 3 weeks to 8 months, with a mean of 2-3 months after initial contact.
The rate of subclinical infection is as high as 40 percent when measured by polymerase chain reaction DNA analysis on genital skin. After the initial clinical manifestation, warts may increase in number and size, or may regress spontaneously (as many as 30 % over 4 months). The rate of long-term regression is unknown.
Even with therapy, recurrence occurs within 3 months in 25-67 percent of cases. Recurrences are often at sites of previous genital warts, attributed to long-lived cells at the site of previous clearance that then reactivate. Infection with high-risk types of HPV and older age patients are risk factors for persistence.
Traditional theories postulated that once a person is infected, HPV remained in the body for a lifetime. However, new studies using sensitive DNA techniques have shown that an HPV cure (with the virus suppressed to levels below what PCR tests can measure) is possible through immunological response.
These studies further concluded that among other genital warts cures, HPVCurative best extracts "inhibited skin papillomas (HPV) and decreased the conversion of papillomas to carcinomas" which resulted in "significant apoptosis (disintegration) of HPV cells in DNA tests" without damaging surrounding healthy tissue.
HPVCurative contains stringently certified organic antiviral plant extracts, which have the ability to destroy the genital wart virus (HPV). The extracts are harvested and distilled by hand for medicinal use -- they are pure and complete. This is essential when creating HPV cures, and it is of critical importance when applying anything to the genitals. To learn more, please go to http://www.forcesofnatureusa.com.
