Persistent HPV Infections - Term Paper Example

?HPV Diagnosis and Treatment Describe the disease – Why is it considered a disease? According to Steben and Duarte-Franco (2007) HPV is a “non-enveloped double-stranded DNA virus,” (p. S2). They go on to explain that there are over 100 different HPV genotypes which have been isolated, and more than 40 of these types infect the epithelial and mucosal lining of the anus and the genitals. They explain that the disease is sexually transmitted, and that the viruses may also infect the mouth and the throat. Persistent HPV infections may cause genital warts, recurrent respiratory papillomatosis (RRP), cervical cancer, and other kinds of cancers, including genital, head and neck, and oropharyngeal cancer. Nearly every case of cervical cancer are caused by HPV, and all cases of genital warts and RRP are caused by HPV. The genital warts appear as small bumps or a group of bumps in the genital area, which may be small or large, raised or flat, or shaped like a cauliflower. These warts may appear within weeks of months after sexual contact with a partner who is infected, even if that partner has no outward signs of the disease. These warts may go away on their own, may remain unchanged, or may multiply or grow larger. The types of HPV that causes the warts are not the same strain that causes the cancers. Cervical cancer is symptomless until it is advanced, so women are encouraged to seek regular screening for cervical cancer. The RRP is a disease where the warts grow in the throat, which can block the airways and cause a hoarse voice or breathing troubles (Steben and Duarte-Franco, 2007). It is considered to be a disease because the mechanisms of the HPV virus change healthy cell tissue into tissue that is infected with lesions. Moreover, HPV is considered to be a disease because it causes other, more serious diseases, especially cervical cancer, as well as cancer that resides in other parts of the body, including the mouth and the throat. Therefore, HPV can be considered to be a somewhat serious concern, in that it could lead to potentially fatal results in the patient. Physiology of the system affected – How does the system normally work? (Diagram of homeostatic regulation of the system) Since the HPV primarily affects the genitals and cervix of the woman, although it can also result in infections in the man, the system that will be examined for the purposes of this essay is the female genitalia. Below is a diagram of a normal female genitalia: The function of the external female reproductive structure is to enable the sperm to enter the body and to protect the internal genital organs from infectious organisms. The labia majora, which is literally “large lips,” is what encloses the protects the external reproductive organs. These are large, fleshy lips, and is the equivalent to the male scrotum. These lips contain sweat and oil-secreting glands. There are also labia minora, which are small lips. These are small lips which may be up to 2” wide. They are just outside the labia minora, and they surround the opening to the vagina and uretha. Bartholin’s glands are another part of the external genitalia, and the Bartholin’s glands are located beside the vaginal opening and produces a fluid secretion. The clitoris is where the two labia minora meet, and this is a small and sensitive protrusion that is comparable to a male penis. It is covered by a fold of skin, and similar to the foreskin at the end of the penis. It is very sensitive to stimulation and may become erect. The vagina is also a part of the female genitalia. It is a canal that joins the cervix, which is the lower part of the uterus, to the outside of the body. This is known as the birth canal. HPV may also affect internal reproductive organs, so there will be some discussion of this as well. In this case, there is a uterus, which is a womb. It is hollow, pear-shaped and is the home for a fetus that is developing. It is divided into the cervix, which is the lower part that goes into the vagina, and the corpus, which is the main body of the uterus. The corpus is what expands to accommodate a growing fetus. The channel through the cervix is what allows the sperm to enter the cervix and allows the menstruation blood to leave the body. Ovaries are also a part of the reproductive system. The ovaries are small and egg shaped, and they are on each side of the uterus. The function of the ovaries is to produce the hormones and the eggs. The fallopian tubes are narrow tubes which attach to the uterus on the upper part of the uterus, and these are tunnels that let the eggs leave the ovaries on their way to the uterus. This is where conception normally occurs. The egg, after meeting the sperm in the fallopian tube, makes its way to the uterus, and then implants on the uterine wall. The HPV virus does not necessarily disrupt the reproductive system. Rather, it attaches lesions to different parts of the reproductive system, especially on the vagina and the cervix. It causes disease on these parts of the female anatomy. If it attacks the cervix and causes cancer, then this would be disruptive to the reproductive system, as the cervix is necessary for a healthy conception. Cellular defect – What has gone wrong? Why? According to Duensing (2000), there is a loss of genomic integrity, and the mechanism for the numeric chromosomal alterations in the HPV. That said, Koutsky (1997), states that the epidemiologic information on the HPV is sparse, because most infections are subclinical and sensitive and reliable tests for detecting HPV are relatively new. The HPV culture cannot be reliably grown in culture, so molecular hybridization tests are used to detect HPV DNA or RNA in clinical specimens. Duensing (2000), states that mitoses with abnormal centrosomes are detected in HPV-associated genital squamous lesions. The most prevalent alteration of the mitoses was tripolar spindle pole arrangement. The normal human keratinocytes (NHKs) that were examined by Duensing (2000) expressed abnormal centrosome synthesis and duplication. The researchers further found that HPV-16 E6 and E7 oncoproteins cooperated to induce centrosome associated defects of mitotic spindle formation. They also found that there were aberrant, multipolar metaphase cells which reflect the immediate effect of the HPV oncogenetic expression. The genomes become unstable through the mechanism of the abnormal centrosome duplication induced by the HPV oncoprotein. They concluded that the cellular mechanism that results from an HPV infection is that there is genomic instability, and abnormal mitoses, so there is an increased risk for chromosome missegregation. Pathophysiology – How does the cellular defect alter normal functioning of the system? According to Steben and Duarte-Franco (2007), there are forty different types and strains of HPV, and they infect the ephithelial and mucosal lining of the anogenital tracts and other area. There are two strains which pose a high risk of causing cervical cancer, the HPV16 and HPV18, and there are two strains which pose a low risk of causing cervical cancer, the HPV6 and the HPV11. The HPV6 and HPV11 are associated with lesions which are relatively benign, such as genital warts and low-grade squamous intraepithelial lesions of the cervix. All cases of genital warts are caused by some strain of HPV, and 90% of genital warts are caused by strains which are classified as either HPV6 or HPV11. Cervical cancer is also caused by HPV, as are other kinds of anogenital and extra anogenital cancers and recurrent respiratory papillomatosis, according to Steben and Duarte-Franco (2007). They also state that in the majority of individuals who have some strain of HPV, there are no symptoms, and that 70% of new infections are resolved within 1 year, and 90% are resolved within 2 years. The median duration of new HPV infections is 8 months. In other cases, the infection persists, and cervical cancer develops over a period of 12-15 years through a series of stages. These researchers further state that whether or not an individual resolves the HPV or the HPV develops into serious lesions or cancer depends upon the individual’s susceptibility and other enabling factors. The HPV induced cervical carcinogenesis occurs by primary infection of the proliferating basal cells of the squamous epithelium, and, if the infection is of a high risk HPV type, if there are co-factors, such as smoking, the HPV infection begins accumulating enough genomic instability and leads to neoplastic transformation of the epithelium. The squamous cell carcinomas are the most commonly occurring form of cervical cancer and these may develop from the CIN I/LSILs. The HSILS or the CIN-II/III lesions may develop within 2-3 years of persistent HPV infection in susceptible individuals, and the viral oncogenes E6 and E7 abrogate cell cycle control and apoptosis mechanisms, which signal the transition from a viral infection to a malignancy (Duarte-Franco, 2007). Signs and Symptoms – Do the symptoms that the patient complains about, the signs that you see, make sense with the cellular defect and the pathophysiology? Yes. The signs which are present are consistent with genital warts, which is the signs which are presented when a patient has a strain of HPV. These warts may be raised or flat, or may look like the top of a cauliflower. These warts may be found inside the vagina or the anus, outside the vagina or the anus or on nearby skin, or on the cervix inside of the body. The warts may also occur on the patient’s lips, mouth, tongue or throat. Moreover, other signs are that there is increased dampness in the genital area that is surrounding the warts, there might be increased vaginal discharge, there might be genital itching, and there might be vaginal bleeding that might occurring during or after sex (Kogan, et al., 2013). The patient was complaining of increased vaginal discharge and the presence of bumps outside the genital area. In this case, a pelvic examination was performed. A magnification, or a colposcopy, was used detect the warts that could not be seen with the naked eye. Moreover, a solution was used, which was comprised of watered down vinegar (acetic acid), and this solution was used to see warts better. Moreover, the patient had an abnormal pap smear. These are all signs and symptoms that show that the patient is currently suffering from an acute case of HPV. Homeostasis – What is the body doing to return to normal? Do lab values indicate this? Do your observations of the patient indicate any compensation? The patient’s body is resolving the HPV infection. This is a common occurrence, as 90% of all HPV infections resolve on their own. This needs to be carefully monitored. The lab values do indicate this, and the observation of the patient indicates compensation. This means that the infection appears to becoming lessened through the passage of time, with fewer lesions which are seen, and a Pap Smear shows that the dysplasia which was previously seen has become less as well. Therefore, it is advisable not to initiate treatment just yet. It might be disruptive to the woman, as she might have to come back for more treatment if the HPV viral lesions are still developing. Moreover, since the situation will most likely resolve itself, it is best to monitor to see if the lesions do actually resolve without further treatment. If the lesions do persist, however, there are treatment protocols which might be undertaken, and the following sections describe what these are. Treatment – How do the medications work (mechanism of action)? Do they treat the cellular defect or are they palliative? Are you treating symptoms rather than the disease? According to Nagai et al. (2000), there are a variety of treatments which can be used for HPV. The four main treatment options are as follows: Watch and wait – since many, if not most, cases of HPV clear up on their own, including cervical dysplasia, precancerous cell changes and cervical intraepithelial neoplasia, then it might be advisable to watch and wait. This would mean that that the woman is advised to come in for regular pap smears, perhaps every six months, and see if her case of HPV clears up on its own. Cryotherapy – the abnormal cells are frozen with liquid nitrogen. Conization – this is a cone biopsy which removes the abnormal areas. LEEP of Loop Electrosurgical Excision Procedure – this is where an electrical current removes the abnormal cells. Prescription cream may also be indicated and may be given by a doctor for the patient to apply at home – these can consist of Podofilox or Condylox, or Imiquimod or Aldara. The Podofilox is used for four weeks, and destroys the wart tissue. In 30% to 60% of cases, however, the warts come back. With Imiquimod or Aldara, the immunity system is boosted so that the body can fight the virus on its own. In this case, between 5% and 20% of cases come back. Wart removal treatment may also be indicated. Trichloracetic acid is a chemical which is applied to the wart’s surface. Surgical removal, which is cutting the cells out with a scalpel. Electrocautery, which is burning the warts off with an electrical current. Laser vaporization is where the warts are excised. Moreover, it is not advisable for the warts to be treated aggressively as they appear, as they could still be emerging. This would necessitate repeat treatment. It is advisable to wait a period of months, then cure all the warts at the same time. In the case of treatment for HPV, it generally is a cure for the disease. This means that it is not simply treating the symptoms of the disease, it is treating the actual disease. Surgical removal may cure the issue in a single visit, and the success rates for the other types of techniques range from 80% to 90%. That said, there are factors which make some warts easier to cure than other ones – one of these factors is that smaller warts respond better to treatment than do larger ones, and warts on moist surfaces respond better than warts on drier surfaces. Patients should be re-evaluated if a specific treatment does not cure the problem in three treatments, or in six treatments by different kinds of techniques. Nagai (2000) studied the persistence of the HPV after therapeutic conization, which is important, because there is a subset of patients who will not necessarily be easily cured of the disease. The patient might be at risk for a disease recurrence if there is HPV DNA that is still detected in the cervix after a therapeutic conization. They studied 74 patients, 58 of which were tested for HPV DNA in the pretreatment cervical lesions, and these patients were enrolled in the study. 56 of the 58 patients had HPV DNA in their primary cervical lesions before conization. These patients were then studied with a mean follow up of 31.8 months. After the treatment, HPV DNA was persistently detected in some 19.6% of the patients, but was negative in the other 80.4% of the patients. They found that 5 of the 11 patients who had persistent HPV DNA developed a recurrence of the disease, while none of the DNA negative patients developed a recurrence. They found that the patients with persistent HPV infection after conization for CIN 3 should be closely followed, because these patients are at risk for a disease recurrence. Therefore, for most patients, there is a cure. The exception is for the patients who have persistent HPV DNA after conization. These patients might not be cured, so they need to be monitored. In that case, the symptoms are being treated, not the disease. That said, there are other issues which influence whether or not the HPV is persistent and causes larger problems, and some of these issues center around the patients themselves. For instance, Rubab (2013) found that tobacco chewing might cause cancerous and precancerous lesions, and that the HPV might have a role in this. What occurs in this mechanism is that the exposure to the oral mucosa causes abrasions inside the mouth that make the abrasions more susceptible to HPV. Since HPV may affect the epithelia cells of the skin, lower genital tract and the oral cavity, this has proved to be a problem. The researchers in this study stated that the oral epithelium is invaded and transformed by the HPV, and that this causes multiple lesions. The most susceptible of the mouth cavity to infection is in the lip, cheek, the floor of the mouth and the soft palate, as these are all areas which are soft and pliable, therefore more susceptible to infection. The HPV then can replicate in the nuclei of the infected cells, which leads to the maturation of the virion in the suprabasal epithelial cell layers. The oral mucosa is similar to the cervical mucosa, according to these researchers, so this is why the HPV finds a good breeding ground in the mouth. The researchers found that there was persistent HPV infection in the oral mucosa, and this increases the risk of developing oral cancer. Therefore, according to this research, the patient has much to do with whether or not there is a cure or if there is a persistent infection that might lead to a malignancy. The patient should be well advised to resist chewing tobacco, because this might lead to a malignancy in the mouth. Conclusion HPV is an issue in that it can lead to malignancies in the mouth, cervix and other areas of the body. The breeding ground for HPV are soft ephithelial tissues. However, the vast majority of HPV cases will resolve on their own. Because of this, it is wise to monitor the patient, and see if the lesions resolve spontaneously. If they do not, then there are wide variety of treatments. Only the most persistent HPV, that remains even after aggressive treatment, are issues which need to be examined for a period of time, because these lesions are a risk factor for cancer. References Aciadious, N., Sutton, C., Mandal, D., Hopkins, R., Zaklama, M., Kitchener, H. (2002) Persistent human papillomavirus infection and smoking increase risk of failure of treatment of cervical intraephithelial neoplasia (CIN). International Journal of Cancer, 98.3, 435-439. Duensing, S., Lee, L., Duensing, A., Basile, J., Piboonniyom, S., Gonzalez, S., Crum, C., & Munger, K. (2000) The human papillomavirus type 16 E6 and E7 defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. PNAS, 97.8: 10002-10007. Kogan, E., Fayzullina, N., Demura, T., Sukhikh, G. (2013) Reparative spheroids in HPV-Associated Chronic Cervicitis. International Journal of BioMedicine, 3.3, 192-196. Nagai, Y., Maehama, T., Asato, T., Kanazawa, K. (2000) Persistence of human papillomavirus infection after therapeutic conization for CIN3: Is it an alarm for disease recurrence? Gyncologic Oncology, 79.2, 294-299. Rubab, Z., Baig, S., Siddiqui, A., Nayeem, A., Salman, M., Qidwai, M., Mallick, R. & Qidwell, S. (2013) Human papilloma virus – role in precancerous and cancerous oral lesions of tobacco chewers. Journal of the Pakistani Medical Association, 63.10: 1295-1304. Read More