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HUMAN PAPILLOMAVIRUS (HPV) is the most common sexually transmitted disease in the United States.1 From 50% to 75% of sexually active adults will develop HPV sometime in their lives. See Understanding HPV. Although many people know that HPV infections are the leading cause of cervical cancer, they might be surprised to learn that HPV is also associated with other kinds of cancer, including cancers of the head and neck, and anal and penile cancers.1
The good news? Although HPV infection is common, many times it resolves spontaneously, especially when it affects the cervix. Even better, many HPV infections can be prevented with a vaccine and changes in sexual behaviors. This article examines cancers linked to HPV and how vaccines can prevent HPV infection in those at risk. Let's start by considering how infection occurs.
Over 100 different types of HPV have been discovered and numbered for identification.2 More than 30 types are transmitted sexually.3 As the name indicates, many HPV viruses can cause papillomas (benign warts). For example, HPV type 1 causes plantar warts, and types 6 and 11 are most associated with benign anogenital warts.2 Other types are strongly associated with cancer. For example, HPV types 16 and 18 cause 70% of cervical cancers.4
HPV viruses can be separated into two main subgroups based on where the virus enters the body, which is either through the cutaneous epithelium or through the mucous membranes of the perineal area.
* Cutaneous HPV infections, which are usually benign and tend to invade cutaneous epithelial tissues, are associated with common warts on the hands and feet, such as plantar warts. The exception is Bowen disease, a type of intraepidermal carcinoma that can develop into invasive squamous cell carcinoma.4,5
* Genital HPV infections tend to infect mucous membranes of the penis, perineum, perianal area, vaginal area, vulva, mouth and throat, and of course the cervix. These are easily spread by sexual activity.
The types of HPV that cause benign anogenital warts appear to be different from the types that result in lingering infections that may evolve into cancer. If anogenital warts occur after sexual contact, about 17% of them resolve without treatment in about 4 months and about 70% of them disappear in about 2 years.6
To reduce transmission of the virus and warts, patients can apply podophyllin, a topical drug.7 Patients should understand that lesions may resolve without treatment, which is expensive, may cause adverse reactions, and isn't always totally effective. An experienced clinician may perform cryosurgery, electrocautery, surgery, or laser therapy, or apply caustic agents.2
Now let's review several cancer types associated with HPV in more detail. See also A closer look at three rare cancers.
Most sexually active women experience HPV infection of the cervix at some point, but most infections are self-limited.1 In some cases, the infection persists and may eventually evolve into cancer.
In 2010 in the United States, about 12,200 new cases of invasive cervical cancer will be diagnosed and about 4,210 women will die from it.8 Although sexual contact (vaginal or anal intercourse or oral sex) is a risk factor for HPV infection, the virus can be transmitted without sexual intercourse. HPV is transmitted by skin-to-skin contact with an area of the body infected with HPV.9
HPV types 16 and 18 have been shown to cause most cases of cervical cancer.9 Although not all cervical cancers are believed to be triggered by HPV, more than 90% of cervical cancer samples contain HPV-related DNA, and most of those specimens are HPV types 16 or 18.10
Premalignant changes found in a cervical biopsy specimen are classified as cervical intraepithelial neoplasia (CIN) 1 (the least abnormal), CIN 2, or CIN 3. Most CIN 1 infections spontaneously resolve.
About 40% to 50% of CIN 2 lesions regress. But because 20% to 30% of CIN 2 lesions advance to high-grade dysplasia, many are treated.6
Less than 40% of CIN 3 lesions regress. About 50% persist and 12% to 15% progress to squamous cell carcinoma.6 See Where can cervical cancer spread?
When CIN 3 progresses to squamous cell carcinoma or adenocarcinoma in situ, the recommended treatment is a modified radical hysterectomy. Some patients want to preserve their fertility: Those with squamous cell carcinoma in situ can opt for cryosurgery, laser surgery, or cold knife conization, whereas patients with adenocarcinoma in situ could choose a cone biopsy. Patients who don't have a hysterectomy require close serial observation and the previously recommended modified radical hysterectomy if the cancer returns. If the cancer is still early stage but larger (up to 5 mm), the patient may be offered a modified radical or radical hysterectomy along with lymph node dissection, or perhaps radiation therapy.11
Fairly early-stage tumors, generally stage I, could also benefit from external beam radiation therapy followed by brachytherapy (internal radiation therapy). For a tumor up to 4 cm, radical hysterectomy should be followed by chemotherapy and radiation.11 However, each added treatment is associated with greater morbidity, including urinary retention, lower extremity lymphedema, and hematologic issues related to the chemotherapy, such as leukocytopenia, thrombocytopenia, and anemia.
For local extension of large tumors, a pelvic exenteration along with chemotherapy and radiation is used. Pelvic exenteration is surgery to remove the organs, tissues, and lymph nodes of the pelvis where cancer has spread, such as the uterus, vagina, bladder, rectum, and parts of the colon.9 Palliative chemotherapy or a clinical trial is an option for women with remote metastasis.
Assess for urinary retention. Some patients with cervical cancer require a suprapubic catheter or self-catheterization, usually temporarily unless they have permanent damage from surgery or other treatments. Excellent skin care is imperative after surgery or radiation therapy. Teach patients how to prevent or manage lower extremity lymphedema, such as by avoiding tight-fitting garments and injuries to the lower extremities.
Anal cancer is fairly rare. The American Cancer Society estimates that in 2010, about 5,260 new cases of anal cancer will be diagnosed and anal cancer will cause about 720 deaths in the United States.8 HPV, particularly types 16 and 18, is associated with more than 90% of anal cancers.12
The main risk factor is exposure to the HPV virus through skin-to-skin contact with an infected body area. In women, vaginal secretions containing the HPV virus can pool during sexual contact and extend from the vagina to the anus. Women who've been previously diagnosed with an HPV infection in the cervix, vagina, or vulva are at high risk for having secretions travel to the anal area.
For men, the virus tends to collect in secretions at the base of the penis and the scrotum during sexual contact, tending to make condoms ineffective against the virus.13
Another important risk factor is assumed to be anal intercourse or contaminated objects placed in the anal canal during sexual contact. Men who have sex with men have high risk rates if they practice receptive anal intercourse.12 Patients may not always report this information.14
Stage I tumors can be treated with a local resection or external beam radiation therapy. Stage II disease can be treated with a radical resection, such as an abdominoperineal resection, in which the anus or rectum is removed and a colostomy is required, or external beam radiation with chemotherapy or sometimes with brachytherapy.15 Stage IV disease is generally treated with external beam radiation and chemotherapy with no intent to cure. Patients with very advanced stage disease or with recurrence may require palliative surgery or chemotherapy and radiation therapy to manage severe pain or bleeding.16
Patients who have radical surgeries for anal cancer may have a permanent colostomy and require the help of a wound, ostomy, and continence nurse (WOCN). External beam radiation to the anal area can cause burning and moist desquamation requiring management by a WOCN. Monitor patients who've had radiation for diarrhea and resulting skin irritation. Monitor them for dehydration and take steps to prevent it, such as administering medications to firm the stools and encouraging oral fluid intake.
In the last decade, some head and neck cancers have been linked to HPV. The usual risk factors for these cancers, most often found in people in their 50s or 60s, are heavy tobacco and alcohol use, but many younger patients who don't conform to this profile have been diagnosed. Their cancer may be related to HPV.17 The most important risk factor for HPV-related head and neck cancers is number of lifetime sexual partners, especially oral sexual partners.
In 2010, about 49,260 patients will be diagnosed with head and neck cancer in the United States, with men outnumbering women about 3 to 1, and about 11,480 patients dying.8 Most of these cancers are head and neck squamous cell carcinoma when diagnosed.
Head and neck cancers can affect any part of the oral cavity (including the lips, anterior two thirds of the tongue, gingiva, floor of the mouth, hard palate, and buccal mucosa), the salivary glands, the paranasal sinuses and nasal cavity, the pharynx, larynx, and lymph nodes in the upper part of the neck.18 From 25% to 30% of these tumors are probably associated with HPV.19
The oropharynx (soft palate, tonsils, and the base of the tongue) is most often affected. About 36% of oropharynx tumors and 22% of oral cavity tumors are related to HPV. Over 90% of the HPV-positive cancers in the oropharynx are related to HPV type 16; the rest are related to HPV types 18, 33, 35, and 45.20
Pathologists have difficulty determining whether these tumors are strictly related to HPV because many patients also use tobacco or alcohol. Interestingly, research studies show that patients with HPV-positive cancers may have twice the overall survival than those with HPV-negative cancers. Although the reason for this isn't known, the makeup of the DNA may be different in tumors caused by HPV, leading to a more favorable reaction to treatment.21
Surgery provides the best outcome for tumors of the oropharynx, especially those of the tonsils and base of the tongue. Often surgery is combined with external beam radiation therapy. Some patients with more advanced disease have been treated with combined chemotherapy and radiation with favorable results; this approach allows preservation of tissues and function as well as fewer adverse effects.22
Surgery is now transoral with much less morbidity than resections that involved incisions in the anterior neck. Transoral robotic resection of tonsillar carcinoma causes less edema and allows quicker recovery. Combined chemotherapy and radiation is used in advanced and recurrent disease.22
After head or neck surgery, assess the patient's airway. A patient with edema may need a tracheotomy. Assess the patient for edema or other surgical changes that could affect the ability to eat. A speech therapist can help patients with eating or speaking. After radiation therapy to the head or neck, the patient's mouth and esophagus may be irritated. Nutritional support may be needed until the inflammation resolves. Patients with mucositis may need specialized care including nutritional support.
Teach patients about chemotherapy or targeted therapies, which zero in on certain cell-related reactions. For instance, these therapies can block the growth of tumors or blood vessels to the tumor. Cetuximab is one targeted therapy used in head and neck cancer to block tumor growth.23
Assess patients for adverse reactions, such as bone marrow suppression, nausea, vomiting, mucositis, and rashes, and signs and symptoms of hypersensitivity reactions. Teach patients about these adverse reactions and how to monitor them at home.
For patients with late-stage cancer, be prepared to provide palliative care or information about clinical trials. Some nurses in academic centers may administer Phase I chemotherapy in clinical trials.
Now let's focus on the good news-many cancers can be prevented.
Two vaccines have been approved to prevent infection with certain types of HPV.
Gardasil. In 2006, the FDA approved the HPV quadrivalent vaccine, recombinant (Gardasil). This was developed to vaccinate against HPV types 6, 11, 16, and 18, which cause many HPV-related cancers and many genital warts.
Gardasil is administered I.M. with follow-up injections 2 and 6 months after the first injection. It's indicated for use in girls and women ages 9 to 26. It's now also indicated in boys and men ages 9 through 26 for the prevention of genital warts caused by HPV types 6 and 11.24 The vaccine can prevent the virus, but it can't help those who are already infected. The current vaccine is 70% to 90% effective against HPV 6, 11, 16, and 18.20 Adverse reactions include headache, fever, nausea, dizziness, injection site pain, edema, erythema, pruritus, and ecchymoses.24
Cervarix. HPV bivalent vaccine, recombinant (Cervarix), was approved by the FDA in 2009. Cervarix was developed to prevent infection from HPV types 16 and 18. Cervarix stimulates the immune system to make antibodies against the virus. It has an adjuvant chemical to allow for longer lasting protection against these types of HPV.25
This vaccine is approved for use in girls and women ages 10 to 25. Cervarix injections are given I.M. with a follow-up injection at 1 and 6 months. Common adverse reactions include pain, erythema, and pruritus at the injection site; fatigue; headaches; myalgia; arthralgia; and gastrointestinal signs and symptoms such as nausea, vomiting, and diarrhea. It can sometimes also cause dizziness.26
Vaccinating patients before their first sexual contact is important because some people can be asymptomatic carriers of HPV. Research studies are continuing to determine whether women and men who are older than the recommended ages can benefit from the vaccine. Data seem to show that the incidence of female genital cancers could be decreased by vaccine. The vaccines may also help reduce the incidence of penile, anal, and head and neck cancers.
Whether they're vaccinated or not, women should still have a Pap test, HPV test, and pelvic exam at least every 3 years, beginning about 3 years after having sexual intercourse for the first time or at age 21, whichever comes first. The other years, they should have a clinical exam by their healthcare practitioner. Women ages 70 or older who have had three normal Pap tests and no abnormal tests in the last 10 years can also stop having Pap tests after a discussion with their healthcare provider.9 Women who have had a hysterectomy can also discontinue Pap testing unless the surgery was done because of cancer or precancer.
Women who have abnormal Pap test results will need further testing or treatment. Precancerous lesions can be treated before they develop into cancer.27
Teach your patients to reduce the risk of getting cervical and other HPV-related cancers by avoiding exposure to HPV. The risk of being infected with HPV increases when people:
* have sex at a young age
* have several sexual partners
* choose a partner who's had many sexual partners
* have sex with uncircumcised males.
To lower the risk of HPV-related cancers, advise your patients to:
* delay having sex for the first time
* choose a partner who's had no or few previous partners
* be in a mutually monogamous relationship
* use condoms with every sex act from start to finish (even though condoms don't fully protect against the transmission of HPV)
* refrain from smoking
* get vaccinated.1,9
Your most important role is to help prevent HPV infection. Start by educating young people and their parents about how to avoid acquiring and transmitting the virus. Encourage the vaccination of young people against HPV. Explain the schedule of injections for vaccination, adverse reactions, and consequences of acquiring the HPV infection. Nurses working in schools or pediatricians' offices should be armed with this information for young people and their parents. Your efforts may help patients ward off some kinds of cancer.
HPV is a virus that can cause warts and other abnormal tissue growths, and can cause dysplastic changes. It can infect the epithelium of the skin and mucous membranes selectively.2 All types of squamous epithelium can be infected by HPV, including cells on the surface of the skin, genitals, anus, mouth, and throat. Most often, the incubation period is 3 to 4 months.2
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