Human papillomavirus

                                                                       Abstract

            In this study of human papillomavirus, we are going to look the viruses that cause HPV, types of HVP, areas mostly affected by the virus, diagnosis, treatment, vaccination as well as preventive measures. Abstinence is the most safest method of preventing the spread of HPV, but fewer people are willing to practice that or in that cause may not have the knowledge that the virus is living in them until later stages. Recent studies show that a high percentage of US population is affected by HPV disease; mostly young women in colleges and high school going girls, little measures are being put in place to stop spreading of this virus. Genital viruses can cause cervical cancer which puts the patients at high risk such as death; it’s recommended that women of reproductive age to undergo regular Pap smear test for early detection and vaccinations for women from 9 years of age to 26. Men who practice anal intercourse are put at risk as well and anal Pap smear is recommended for them.

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            Papillomavirus are highly species that infect human beings and are nonenveloped viruses of icosahedral symmetry with at least 72 capsomeres that surround a genome containing double-stranded circular DNA with an average of 8000 base pairs. These viruses have to mode of replication, one is runaway type of papillomavirus also known as vegetative which replicates in more differentiated cells to generate progery virus, the other is a stable replication of the episomal genome in basal cells. Expression of viral genes is closely linked to the state of cellular differentiation although all cells of a lesion contains viral gene. Virus production only occurs at the pethelial surface as the infected keratinocyte leaves the basal layer when basal cells in the host are exposed to infection during sexual intercourse or after minor skin abrasions which causes disturbances in epithelial barrier. This virus can survive for many months without a host at low temperatures; therefore a person with plantar warts can spread the virus even by walking barefoot. HPV genome exist normally as a circular episomal DNA separate the host cell nucleus in low risk HPV lesion such as those associated with types 6 and 11 and genomes of high-risk HVP types such as 16 and 18, intergrate into the host cell DNA in malignant transformation ( Gearhart & Randall, 2007, p.2).

            There are over 40 types of human papillomavirus that infect anogenital tract of men and women and causes condylomata acuminate also known as venereal warts which leads to precancerous changes in the urine cervix and causes cervical cancer. This type of HPV causes cervical cancer in women and penile cancer in men.  Genital warts and HPV infection are transmitted through sexual intercourse with an infected partner and the risk of infection increases as the number of sexual partners increase. The most common types of HPV that affect the anogenital tract are HPV- 6, 11, 16 and 18. Types 6 and 11 of HPV are associated with benign lesions like genital warts and mild dysplasia of the cervix the tern know as “low- risk” HPV type. In contrast, HPV 16 and 18 belong to the “high-risk” group and these HPVs are found in most of the cervical and anogenital cancers as well as severe dysplasia of the cervix. HPV-5 and 8 infect the skin and cause warts in the body and for people with conditions such as epidermodysplasia verruciformis causes skin cancer (Stoppler, 2008, p.1)

            HPV infection alone does not cause malignant transformation of infected tissue, a number of factors contribute to this such as tobacco use, pregnancy, ultraviolet radiation, folate deficiency and immune suppression. The table below lists a variety of diseases and the associated HPV subtypes according to Gearhart & Randall.

                               Nongenital Cutaneous Disease
HPV Type
Common warts ( vulgaris)

Warts (Nongenital)
1, 2, 4, 26, 27, 29, 41, 57, 64
Plantar warts (myrmecias)

Warts, Plantar
1, 2, 4, 63
Flat warts (verrucae plana)
3, 10, 27, 28, 38, 41, 49
Butcher’s warts (common warts of people who handle meat, poultry, and fish)
1, 2, 3, 4, 7, 10, 28
Mosaic warts
2, 27, 57
Ungual squamous cell carcinoma
16
Epidermodysplasia verruciformis (benign)

Epidermodysplasia Verruciformis
2, 3, 10, 12, 15, 19, 36, 46, 47, 50
Epidermodysplasia verruciformis (malignant or benign)
Epidermodysplasia Verruciformiss
5, 8, 9, 10, 14, 17, 20, 21, 22, 23, 24, 25, 37, 38
Nonwarty skin lesions
37, 38
Anogenitical Disease
HPV Type
Condylomata acuminata
6, 11, 30, 42, 43, 44, 45, 51, 52, 54
Bowenoid papulosis
Bowenoid Papulosis
16, 18, 34, 39, 42, 45
Bowen disease
16, 18, 31, 34
Giant condylomata (Buschke-Löwenstein tumors)
Giant Condylomata Acuminata of Buschke and Löwenstein
6, 11
Unspecified intraepithelial neoplasia
30, 34, 39, 40, 53, 57, 59, 61, 62, 64, 66, 67, 68, 69
Low-grade intraepithelial neoplasia
6, 11, 43
Intermediate intraepithelial neoplasia
31, 33, 35, 42, 45, 51, 52
High-grade intraepithelial neoplasia
16, 18, 56, 58
Carcinoma of vulva
Malignant Vulvar Lesionss
6, 11, 16, 18
Carcinoma of vagina
16
Carcinoma of cervix
Cervical Cancer
16, 18, 31
Carcinoma of anus
16, 31, 32, 33
Carcinoma in situ of penis (erythroplasia of Queyrat)
16
Carcinoma of penis
16, 18

Nongenital Mucousal Disease
HPV Type
Respiratory papillomatosis
Recurrent Respiratory Papillomatosis
6, 11
Squamous cell carcinoma of the lung
6, 11, 16, 18
Laryngeal papilloma
6, 11, 30
Laryngeal carcinoma
16, 18
Maxillary sinus papilloma
57
Squamous cell carcinoma of the sinuses
16, 18
Conjunctival papillomas
6, 11
Conjunctival carcinoma
16
Oral focal epithelial hyperplasia (Heck disease)
13, 32
Oral carcinoma
16, 18
Oral leukoplakia
16, 18
Squamous cell carcinoma of the esophagus
16, 18

            Genital human papillomavirus (HPV) is asexuality transmitted disease caused by Human Papillomavirus which affects the skin and mucous membranes in both men and women. People get infected through genital contact during vaginal and anal sex. People having this infection can not even know that they have it as you cannot see it and they may be passing on to other people without their knowledge. This type of virus affects parts of the genital areas such as the skin of the penis, anus, vulva and the linings of the vagina, cervix and rectum. Pregnant women with HPV can pass this virus to the baby during delivery; in this case the baby may develop warts in the throat a condition called recurrent respiratory papillomatosis (RRP). Certain types of HPV cause genital warts and cervical cancer in areas of vulva, vagina, anus and penis but in most cases this virus does not cause symptoms. The body immune system clears HPV naturally within two years (Centers for Disease Control and Prevention, 2008).

            Genital warts affect the vaginal area, anus, vulva, on the cervix, the penis, scrotum, groin or thighs characterized by small to groups of bumps and sometimes cauliflower in shape. They appear within weeks after sexual contact with an infected person and if left untreated they may increase the size in number or may go away by themselves. Cervical cancer does not have symptoms until at later stages when it’s quite advanced and women are advised to undergo regular screening for early detection. HPV-related cancers on the other hand may not have signs or symptoms until they are advanced. HPV caused the normal cells on infected skin and mucous membrane to turn abnormal that takes the form of genital warts. Sometimes this clears by itself but in cases of high risk infection which may not have been cleared by the immune system overtime, may turn abnormal cells in to cancer (Centers for Disease Control and Prevention, 2008).

            HPV is considered the most common sexual-transmitted infection in the U.S and studies show that at least 75% of the re-productive-age population has been infected once in their life time with sexually-transmitted HPV. It’s believed that every year in the US, over 6 million people become infected and approximately 50% of them are between the ages of 15 and 25 according to Centre for disease control. This infection can be transmitted by skin to skin genital contact or by rubbing. Women are considered to be the most at risk are the ones with multiple sex partners. During sexual intercourse the virus enters the body through layers of the skin, cervix or vagina and once they have been penetrated, the virus attacks the cells and multiplies. Once they become established in these areas they become multiply to become a genital wart. Since the virus is located on the testicles or vulva of the female, use of condom may not fully prevent the spread of the virus. A person cam become infected with more than one type of virus and one of these viruses can cause pre-cancerous changes in the cervix and this puts them at the risk of developing anus and prostate cancer (Ward, 2007; Borshat ; Hausen, 1986).

            HPV can be prevented by a vaccine that protects females from this viruses that cause cervical cancers and genital warts from the ages of 13 to 26. Use of condoms is recommend as well for sexually active people, however the prevention is not fully guaranteed as  it does not fully cover all areas son avoiding sexual activity will help prevent this virus. On the other hand men do not have a vaccine to prevent HPV- related diseases but studies are being done if the women vaccine can be safe for men as well. Yearly anal pap test for gay and bisexuals and HIV-positive persons because anal cancer is more common in them. More studies on the way being done to screen for penile and anal cancer for patients who may be at high risk of those related diseases. To protect the babies delivered by mothers with genital warts, cesarean delivery is not recommended (Centers for Disease Control and Prevention, 2008).

            Women with history of a cervical high-grade squamous intraepithelial lesion (HGSIL) or invasive squamous cell carcinoma (SCC) of the cervix are at increased risk of getting HPV particularly vaginal carcinoma and anal carcinoma. Women are the most affected by these viruses and in particular patients who are immunosuppressed have much higher incidence of EV-HPV infection. Nongenital cutaneous warts are common among white people whereas cervical cancer death rates are reported by the US to be higher among black women. College-age womwn and girls seem to have higher anolegenital mucosal HPV infection, whereas nongenital cutaneous warts are common among teenagers and also in adults who work in meat, poultry and fish industries (Gearhart ; Randall, 2007, p.2).

             Genital warts are diagnosed by visual inspection and acetic acid test may be done to help identify the warts. Routine Pap test can help identify high-risk HPV types that cause cervical changes and cancer and this can help prevention. A healthy immune system can help fight HPV naturally. Cervical cancer patients may undergo surgery, radiation therapy and chemotherapy to help treat the virus. Visible genital warts can be removed by medication application provided by health care providers. To determine whether a person is infected with HPV involved test to identify the genetic material of the virus. Genital warts are sometimes associated with itching, burning or tenderness. Women who have genital warts inside their vagina may bleed during sexual intercourse or they may experience an abnormal vaginal discharge and in some cases bleeding or urinary obstruction may occur (Stoppler, 2008, p.3).

            Liquid based pap smear known as Thin Prep and SurePath are the only to methods that show good results for sensitivity of the cervical cytology screening as it enables easy testing for HPV and approved by the US Food and Drug Administration (FDA). HPV DNA typing has two methods of testing which are highly effective in detection included are; Hybrid Capture II (HC II) and the polymerase chain reaction (PCR) enzyme immunosorbent assay. Pap smear test done should contain samples of cells from the electocervix, transformation zone and endocervical canal on a patient not menstruating. If the patient has a cervicovaginal infection with a mucopurulent discharge in the vagina the test should be performed after the bacteria infection has resolved. If in any case the test must be done, then the discharge should be gently cleared with a saline-moistened cotton swab. The tests in question require a sample tissue of the vagina, vulva and perenial region that are suspicious for intraephelial neoplasia. Men who participate in receptive intercourse, Pap smear should be performed on them as well as they are at a high risk of contracting the virus as well (Gearhart ; Randall, 2007, p.5).

            There is no cure that can eradicate HPV infection but the only available treatment is to remove the lesions caused by the virus but this does not prevent the spread of the virus as the genital warts frequently reoccur. The first treatment administered is a 0.5% solution or gel of podofilox (Condylox), this treatment is applied to the warts twice per day for three days and then followed by 4 days without treatment. This kind of treatment should be fooled up to 3-4 weeks or until lesions are gone. A 5% cream of Aldara should be applied by the patient as an alternative to podofilox three times a week at bedtime and then washed up after 6-10 hours with mild soap and water until the lesions are gone. An experienced physician can place a small amount of a 10-25% solution of podophyllin resin on the lesion for a period of hours and then washing of the solution, this should be repeated weekly until the genital warts are completly gone and also application of a 80-90% solution of trichloroacetic acid (TCA) or bichloracetic acid (BCA) also applied weekly. Injection of 5-flurouracil epinephrine gel and interferon alpha into the lesions has shown effective results in treating genital warts. Cryotherapy every 1 to 2 weeks, surgical removal of the lesions and laser surgery has been effective in removing warts (Stoppler, 2008, p.4).

            Keratolytics are the only agents that have showed good results in treating nongenital cutaneous warts such as imiquimod which is a powerful cytokine inducer that stimulates the interferon alfa, tumor necrosis factor and interleukin (IL)-1, IL-6 and IL-8. This treatment is applied on the external anogenital wart s and condyloma acuminatum for 3 times a week for 6-10 hours. Interferon alfa is produced by recombinant DNA technology or by collection from pooled human leukocytes which has potent immunomodulatory and direct antiviral effects as well. This is injected into the base of each wart using a dose of 250,000 IU per wart with improved results starts showing in a period of 4-8 weeks. 5-Fluorouracil treatment is an antimetabolite that intereferes with the synthesis of DNA and RNA and creates a thymine deficiency resulting in unbalanced growth and death of a cell. Keratolytics is powerful agents that rapidly penetrate and chemically cauterize skin, keratin and other tissues with application of 80-90% solution weekly. Salicylic acid is easily found on pharmacies and can be used as a primary treatment (Gearhart ; Randall, 2007, p.6).

            Surgical procedures and medical training may be used as reoccurrence of warts is less common as compared to medical therapies. Included are cryosurgery, electrodesiccation or loop electrosurgical excision procedure (LEEP) or in some cases simple procedures may be used like excision with a scapel, scissors or curette. Other procedures include carbon dioxide laser ablation, Cavitron Ultrasonic Surgical Aspiration (CUSA) and Mohs surgery.  Cryosugery involves freezing the intercellular water resulting to cellular destruction, used commonly in simple cutaneous warts and low-grade cervical intraepithelial neoplasia (CIN I), however not recommended for vaginas. Electrosurgery modalities use high-frequency current to cut and coagulate warts. This may be used to remove large genital warts and to treat cervical SILs. Simple surgical procedures such as excision with a scalpel, scissors or curette can be performed to remove warts and treat SILs of the genital tract under local anesthesia. Refractory HPV disease or extensive warts of the anogenital and mucosal category can be treated by carbon dioxide laser vaporization. Cavitron Ultrasonic Surgical Aspirator destroys the tissue through heat and cavitation and this has been used for cytoreduction of intra-abdominal tumors because of its ability to remove epithelium without damaging the underlying tissue (Gearhart ; Randall, 2007, p.6).

            Vaccination is another form of prevention which protects against four major types of HPV that causes cervical cancer and genital warts and this vaccination may start with girls young form 9 years as it is important before their sexual contact but when a woman is already infected the vaccine may not help the prevention. Women and girls from 13-26 should also be given this vaccination, if they were not given when they were younger in 3-dose series in the following order; 1st Dose now, 2nd Dose 2 month after Dose 1 and 3rd Dose 6 month after Dose 1. Girls and women who had ever had life threatening allergic reaction to yeast and other components of HPV vaccine should not get the vaccine and pregnant women as well. Breast feeding mothers may get the vaccine as this will not affect the baby and People with severe illness could wait to heal before the vaccination is given to them (Centers for Disease Control and Prevention, 2007, p.2).

                                                           Conclusion

            People with multiples partners should be advised the dangers that entails the behavior as they put their health at high risk Those who are already infected with HPV virus,  need to be counseled about the risk of spreading HPV and the appearance of the lesions. Use of condoms may not effectively prevent the spread of the infection, in this case abstinence is highly recommended but few people are willing to do so. Vaccination in prevention of HPV is not commonly practiced among people, as this is the most effective in prevention of the virus. Campaigns in schools and colleges to educate young people on HPV sexual transmitted diseases is important  as they will have general knowledge of what it is, prevention measures and seek medical attention early. Good care for delivery mothers should be provided to avoid transmitting the virus to the new born baby.

                                                           References

Boshart, M., ; Hausen, Z, H. (1986). Human papillomaviruses in Buschke-Lowenstein tumors: physical state of the DNA and identification of a tandem duplication in the           noncoding region of a human papillomavirus 6 subtype, 58(3):963-6.

Centers for Disease Control and Prevention. (2008, October, 10). Genital HPV Infection-CDC    Fact Sheet. Retreived September 16, 2008,

            from;http://www.cdc.gov/STD/HPV/STDFact-HPV.htm

Centers for Disease Control and Prevention. (2007). Vaccine Information Statement          (interim); Human Papillomavirus (HPV) Vaccine, 1-2.

Gearhart, P, A., ; Randall, C, T. (2007). Human Papillomavirus, 1-11. Retrieved on September   16, 2008, from; http://www.emedicine.com/MED/topic1037.htm

Stoppler, M, C. (2008). Human Papillomaviruses (HPVs) and Genital Warts. Medicinenet, 1-7.

            Retrieved September 16, 2008,

            From; http://www.medicinenet.com/genital_warts_in_women/article.htm

Ward, S. ( November, 2007). Human Papilloma Virus (Vaginal Genital Warts). Human Papilloma           Virus (HPV).

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