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14-September-2008 11:27:25 - cancer The references used in this article may be clearer with a different or consistent style of citation, footnoting, or external linking. Cervical cancer Classification and external resources Histopathologic image HE stain of carcinoma in situ, stage 0. ICD-10 C53 ICD-9 180 OMIM 603956 DiseasesDB 2278 MedlinePlus 000893 eMedicine med/324 radio/140 MeSH D002583 This large squamous carcinoma bottom of picture has obliterated the cervix and invaded the lower uterine segment. The uterus also has a round leiomyoma up higher. This large squamous carcinoma bottom of picture has obliterated the cervix and invaded the lower uterine segment. The uterus also has a round leiomyoma up higher. Cervical cancer is malignant cancer of the cervix uteri or cervical area. It may present with vaginal bleeding but symptoms may be absent until the cancer is in its advanced stages. Treatment consists of surgery including local excision in early stages and chemotherapy and radiotherapy in advanced stages of the disease. Pap smear screening can identify potentially precancerous changes. Treatment of high grade changes can prevent the development of cancer. In developed countries, the widespread use of cervical screening programs has reduced the incidence of invasive cervical cancer by 50% or more. Human papillomavirus HPV infection is a necessary factor in the development of nearly all cases of cervical cancer.1 HPV vaccine effective against the two most common cancer-causing strains of HPV has been licensed in the U.S. and the EU. These two HPV strains together are currently responsible for approximately 70%23 of all cervical cancers. Since the vaccine only covers some high-risk types, women should seek regular Pap smear screening, even after vaccination.4 Contents 1 Classification 2 Signs and symptoms 3 Causes 3.1 Human papillomavirus infection 3.2 Cofactors 4 Diagnosis 4.1 Biopsy procedures 4.2 Pathologic types 4.3 Staging 5 Treatment 6 Prevention 6.1 Awareness 6.2 Screening 6.3 Preventive Vaccination 6.4 Condoms 7 Prognosis 8 Epidemiology 9 History 10 References and Notes 11 External links Classification Cervical cancer is a carcinoma, typically composed of squamous cells, and is similar in some respects to squamous cell cancers of the head and neck and anus. All three of these diseases may be associated with human papillomavirus infection. Signs and symptoms The early stages of cervical cancer may be completely asymptomatic.5 Vaginal bleeding, contact bleeding or rarely a vaginal mass may indicate the presence of malignancy. Also, moderate pain during sexual intercourse and vaginal discharge are symptoms of cervical cancer. In advanced disease, metastases may be present in the abdomen, lungs or elsewhere. Symptoms of advanced cervical cancer may include: loss of appetite, weight loss, fatigue, pelvic pain, back pain, leg pain, single swollen leg, heavy bleeding from the vagina, leaking of urine or feces from the vagina,6 and bone fractures. Causes Human papillomavirus infection The most important risk factor in the development of cervical cancer is infection with a high-risk strain of human papillomavirus. The virus cancer link works by triggering alterations in the cells of the cervix, which can lead to the development of cervical intraepithelial neoplasia, which can lead to cancer. Women who have many sexual partners or who have sex with men or women who had many partners have a greater risk.78 More than 250 types of HPV are acknowledged to exist some sources indicate more than 200 subtypes.910 Of these, 15 are classified as high-risk types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82, 3 as probable high-risk 26, 53, and 66, and 12 as low-risk 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108,11 but even those may cause cancer. Types 16 and 18 are generally acknowledged to cause about 70% of cervical cancer cases. Together with type 31, they are the prime risk factors for cervical cancer.12 Genital warts are caused by various strains of HPV which are usually not related to cervical cancer. The medically accepted paradigm, officially endorsed by the American Cancer Society and other organizations, is that a patient must have been infected with HPV to develop cervical cancer, and is hence viewed as a sexually transmitted disease, but most women infected with high risk HPV will not develop cervical cancer.13 Use of condoms reduces, but does not always prevent transmission. Likewise, HPV can be transmitted by skin-to-skin-contact with infected areas. In males, HPV is thought to grow preferentially in the epithelium of the glans penis, and cleaning of this area may be preventative. Cofactors The American Cancer Society provides the following list of risk factors for cervical cancer: human papillomavirus HPV infection, smoking, HIV infection, chlamydia infection, dietary factors, hormonal contraception, multiple pregnancies, exposure to the hormonal drug diethylstilbestrol DES and a family history of cervical cancer.7 There is a possible genetic risk associated with HLA-B7.citation needed Despite the development of an HPV vaccine, some researchers argue that routine neonatal male circumcision is an acceptable way to lower the risk of cervical cancer in their future female sexual partners. Others maintain that the benefits do not outweigh the risks and/or consider the removal of healthy genital tissue from infants to be unethical as it cannot be reasonably assumed that a male would choose to be circumcised. There has not been any definitive evidence to support the claim that male circumcision prevents cervical cancer, although some researchers say there is compelling epidemiological evidence that men who have been circumcised are less likely to be infected with HPV.14 However, in men with low-risk sexual behaviour and monogamous female partners, circumcision makes no difference to the risk of cervical cancer.15 Diagnosis Biopsy procedures While the pap smear is an effective screening test, confirmation of the diagnosis of cervical cancer or pre-cancer requires a biopsy of the cervix. This is often done through colposcopy, a magnified visual inspection of the cervix aided by using an acetic acid e.g. vinegar solution to highlight abnormal cells on the surface of the cervix. Further diagnostic procedures are loop electrical excision procedure LEEP and conization, in which the inner lining of the cervix is removed to be examined pathologically. These are carried out if the biopsy confirms severe cervical intraepithelial neoplasia. Pathologic types Cervical intraepithelial neoplasia, the precursor to cervical cancer, is often diagnosed on examiniation of cervical biopsies by a pathologist. Histologic subtypes of invasive cervical carcinoma include the following:1617 squamous cell carcinoma about 80-85% adenocarcinoma adenosquamous carcinoma small cell carcinoma neuroendocrine carcinoma Non-carcinoma malignancies which can rarely occur in the cervix include melanoma lymphoma Note that the FIGO stage does not incorporate lymph node involvement in contrast to the TNM staging for most other cancers. For cases treated surgically, information obtained from the pathologist can be used in assigning a separate pathologic stage but is not to replace the original clinical stage. For premalignant dysplastic changes, the CIN cervical intraepithelial neoplasia grading is used. Staging Cervical cancer is staged by the International Federation of Gynecology and Obstetrics FIGO staging system, which is based on clinical examination, rather than surgical findings. It allows only the following diagnostic tests to be used in determining the stage: palpation, inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous urography, and X-ray examination of the lungs and skeleton, and cervical conization. The TNM staging system for cervical cancer is analogous to the FIGO stage. Stage 0 - full-thickness involvement of the epithelium without invasion into the stroma carcinoma in situ Stage I - limited to the cervix IA - diagnosed only by microscopy; no visible lesions IA1 - stromal invasion less than 3 mm in depth and 7 mm or less in horizontal spread IA2 - stromal invasion between 3 and 5 mm with horizontal spread of 7 mm or less IB - visible lesion or a microscopic lesion with more than 5 mm of depth or horizontal spread of more than 7 mm IB1 - visible lesion 4 cm or less in greatest dimension IB2 - visible lesion more than 4 cm Stage II - invades beyond cervix IIA - without parametrial invasion, but involve upper 2/3 of vagina IIB - with parametrial invasion Stage III - extends to pelvic wall or lower third of the vagina IIIA - involves lower third of vagina IIIB - extends to pelvic wall and/or causes hydronephrosis or non-functioning kidney IVA - invades mucosa of bladder or rectum and/or extends beyond true pelvis IVB - distant metastasis Treatment Microinvasive cancer stage IA is usually treated by hysterectomy removal of the whole uterus including part of the vagina. For stage IA2, the lymph nodes are removed as well. An alternative for patients who desire to remain fertile is a local surgical procedure such as a loop electrical excision procedure LEEP or cone biopsy.18 If a cone biopsy does not produce clear margins,19 one more possible treatment option for patients who want to preserve their fertility is a trachelectomy.20 This attempts to surgically remove the cancer while preserving the ovaries and uterus, providing for a more conservative operation than a hysterectomy. It is a viable option for those in stage I cervical cancer which has not spread; however, it is not yet considered a standard of care,21 as few doctors are skilled in this procedure. Even the most experienced surgeon cannot promise that a trachelectomy can be performed until after surgical microscopic examination, as the extent of the spread of cancer is unknown. If the surgeon is not able to microscopically confirm clear margins of cervical tissue once the patient is under general anesthesia in the operating room, a hysterectomy may still be needed. This can only be done during the same operation if the patient has given prior consent. Due to the possible risk of cancer spread to the lymph nodes in stage 1b cancers and some stage 1a cancers, the surgeon may also need to remove some lymph nodes from around the uterus for pathologic evaluation. A radical trachelectomy can be performed abdominally22 or vaginally23 and there are conflicting opinions as to which is better.24 A radical abdominal trachelectomy with lymphadenectomy usually only requires a two to three day hospital stay, and most women recover very quickly approximately six weeks. Complications are uncommon, although women who are able to conceive after surgery are susceptible to preterm labor and possible late miscarriage.25 It is generally recommended to wait at least one year before attempting to become pregnant after surgery.26 Recurrence in the residual cervix is very rare if the cancer has been cleared with the trachelectomy.21Yet, it is recommended for patients to practice vigilant prevention and follow up care including pap screenings/colposcopy, with biopsies of the remaining lower uterine segment as needed every 3-4 months for at least 5 years to monitor for any recurrence in addition to minimizing any new exposures to HPV through safe sex practices until one is actively trying to conceive. Early stages IB1 and IIA less than 4 cm can be treated with radical hysterectomy with removal of the lymph nodes or radiation therapy. Radiation therapy is given as external beam radiotherapy to the pelvis and brachytherapy internal radiation. Patients treated with surgery who have high risk features found on pathologic examination are given radiation therapy with or without chemotherapy in order to reduce the risk of relapse. Larger early stage tumors IB2 and IIA more than 4 cm may be treated with radiation therapy and cisplatin-based chemotherapy, hysterectomy which then usually requires adjuvant radiation therapy, or cisplatin chemotherapy followed by hysterectomy. Advanced stage tumors IIB-IVA are treated with radiation therapy and cisplatin-based chemotherapy. On June 15, 2006, the US Food and Drug Administration approved the use of a combination of two chemotherapy drugs, hycamtin and cisplatin for women with late-stage IVB cervical cancer treatment.27 Combination treatment has significant risk of neutropenia, anemia, and thrombocytopenia side effects. Hycamtin is manufactured by GlaxoSmithKline. Prevention Awareness According to the US National Cancer Institute's 2005 Health Information National Trends survey, only 40% of American women surveyed had heard of human papillomavirus HPV infection and only 20% had heard of its link to cervical cancer.28 In 2008 an estimated 3,870 women in the US will die of cervical cancer, and around 11,000 new cases are expected to be diagnosed.29 Screening The widespread introduction of the Papanicolaou test, or pap smear for cervical cancer screening has been cred with dramatically reducing the incidence and mortality of cervical cancer in developed countries.5 Abnormal pap smear results suggest the presence of cervical intraepithelial neoplasia premalignant changes in the cervix before a cancer has developed, allowing for further workup. Recommendations for how often a Pap smear should be done vary from once a year to once every five years. The American Cancer Society recommends that cervical cancer screening should begin approximately three years after the onset of vaginal intercourse and/or no later than twenty-one years of age.30 If premalignant disease or cervical cancer is detected early, it can be treated relatively noninvasively, and without impairing fertility. Until recently the pap smear has remained the principal technology for preventing cervical cancer. However, following a rapid review of the published literature, originally commissioned by NICE 31, liquid based cytology has been incorporated within the UK national screening programme. Although it was probably intended to improve on the accuracy of the pap test, its main advantage has been to reduce the number of inadequate smears from around 9% to around 1% 3. This reduces the need to recall women for a further smear. Automated technologies have been developed with the aim of improving on the interpretation of smears, normally carried out by cytotechnicians. Unfortuantely these on the whole have proven less useful; although the more recent reviews suggest that generally they may be no worse than human interpretation 32. The HPV test is a newer technique for cervical cancer triage which detects the presence of human papillomavirus infection in the cervix. It is more sensitive than the pap smear less likely to produce false negative results, but less specific more likely to produce false positive results and its role in routine screening is still evolving. Since more than 99% of invasive cervical cancers worldwide contain HPV, some researchers recommend that HPV testing be done together with routine cervical screening.12 But, given the prevalence of HPV around 80% infection history among the sexually active population others suggest that routine HPV testing would cause undue alarm to carriers. HPV testing can reduce the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cervical cancer detected by subsequent screening tests among women 32-38 years old according to a randomized controlled trial.33 The relative risk reduction was 41.3%. For patients at similar risk to those in this study 63.0% had CIN 2-3 or cancer, this leads to an absolute risk reduction of 26%. 3.8 patients must be treated for one to benefit number needed to treat = 3.8. Click here to adjust these results for patients at higher or lower risk of CIN 2-3. Preventive Vaccination Main article: HPV vaccine Merck Co. has developed a vaccine against four strains of HPV 6,11,16,18, called Gardasil. It is now on the market after receiving approval from the US Food and Drug Administration on June 8, 2006.2 Gardasil has also been approved in the EU.34 GlaxoSmithKline has developed a vaccine called Cervarix which has been shown to be 100% effective in preventing HPV strains 16 and 18 and is effective for more than four years.35 Cervarix has been approved some places and is in approval process elsewhere.36 Neither Merck Co. nor GlaxoSmithKline invented the vaccine. The vaccine's key developmental steps are claimed by the National Cancer Institute in the US, the University of Rochester in New York, Georgetown University in Washington, DC, Dartmouth College in Hanover, NH, and the Queensland University in Brisbane, Australia. Both Merck Co. and GlaxoSmithKline have licensed patents from all of these parties.37 Together, HPV types 16 and 18 currently cause about 70% of cervical cancer cases. HPV types 6 and 11 cause about 90% of genital wart cases. HPV vaccines are targeted at girls and women of age 9 to 26 because the vaccine only works if given before infection occurs; therefore, public health workers are targeting girls before they begin having sex. The use of the vaccine in men to prevent genital warts and interrupt transmission to women is initially considered only a secondary market. The high cost of this vaccine has been a cause for concern. Several countries have or are considering programs to fund HPV vaccination. Condoms Condoms may also be useful in treating potentially precancerous changes in the cervix. Exposure to semen appears to increase the risk of precancerous changes CIN 3, and use of condoms helps to cause these changes to regress and helps clear HPV.38 One study suggests that prostaglandin in semen may fuel the growth of cervical and uterine tumours and that affected women may benefit from the use of condoms.3940 Prognosis Prognosis depends on the stage of the cancer. With treatment, the 5-year relative survival rate for the earliest stage of invasive cervical cancer is 92%, and the overall all stages combined 5-year survival rate is about 72%. These statistics may be improved when applied to women newly diagnosed, bearing in mind that these outcome may be partly based on the state of treatment five years ago when the women studied were first diagnosed.29 With treatment, 80 to 90% of women with stage I cancer and 50 to 65% of those with stage II cancer are alive 5 years after diagnosis. Only 25 to 35% of women with stage III cancer and 15% or fewer of those with stage IV cancer are alive after 5 years.41 According to the International Federation of Gynecology and Obstetrics, survival improves when radiotherapy is combined with cisplatin-based chemotherapy.42 As the cancer metastasizes to other parts of the body, prognosis drops dramatically because treatment of local lesions is generally more effective than whole body treatments such as chemotherapy. Interval evaluation of the patient after therapy is imperative. Recurrent cervical cancer detected at its earliest stages might be successfully treated with surgery, radiation, chemotherapy, or a combination of the three. Thirty-five percent of patients with invasive cervical cancer have persistent or recurrent disease after treatment.43 Average years of potential life lost from cervical cancer are 25.3 SEER Cancer Statistics Review 1975-2000, National Cancer Institute NCI. Approximately 4,600 women were projected to die in 2001 in the US of cervical cancer DSTD, and the annual incidence was 13,000 in 2002 in the US, as calculated by SEER. Thus the ratio of deaths to incidence is approximately 35.4%. Regular screening has meant that pre cancerous changes and early stage cervical cancers have been detected and treated early. Figures suggest that cervical screening is saving 5,000 lives each year in the UK by preventing cervical cancer.44 About 1,000 women per year die of cervical cancer in the UK. Epidemiology Worldwide, cervical cancer is the fifth most deadly cancer in women.45 It affects about 1 per 123 women per year and kills about 9 per 100,000 per year.citation needed In the United States, it is only the 8th most common cancer of women. In 1998, about 12,800 women were diagnosed in the US and about 4,800 died.5 Among gynecological cancers it ranks behind endometrial cancer and ovarian cancer. The incidence and mortality in the US are about half those for the rest of the world, which is due in part to the success of screening with the Pap smear.5 In Great Britain, the incidence is 8.8/100,000 per year 2001, similar to the rest of Northern Europe, and mortality is 2.8/100,000 per year 2003 Cancer Research UK Cervical cancer statistics for the UK. With a 42% reduction from 1988-1997 the NHS implemented screening programme has been highly successful, screening the highest risk age group 25-49 years every 3 years, and those ages 50-64 every 5 years. Worldwide it is estimated that there are 473,000 cases of cervical cancer, and 253,500 deaths per year.46 History 400 BCE - Hippocrates: cervical cancer incurable 1925 - Hans Hinselmann: invented colposcope 1928 - Papanicolaou: developed Pap technique 1941 - Papanicolaou and Trout: Pap screening 1946 - Ayer: spatula to scrape the cervix 1976 - Zur Hausen and Gisam: found HPV DNA in cervical cancer and warts 1988 - Bethesda System for Pap results developed Epidemiologists working in the early 20th century noted that: Cervical cancer was common in female sex workers. It was rare in nuns, except for those who had been sexually active before entering the convent. Rigoni in 1841 It was more common in the second wives of men whose first wives had died from cervical cancer. It was rare in Jewish women.47 In 1935, Syverton and Berry discovered a relationship between RPV Rabbit Papillomavirus and skin cancer in rabbits. HPV is species specific and therefore cannot be transmitted to rabbits This led to the deduction that cervical cancer could be caused by a sexually transmitted agent. Initial research in the 1950s and 1960s put the blame on smegma e.g. Heins et al 195848 , but it wasn't until the 1970s that human papillomavirus HPV was identified. A description by electron microscopy was given earlier in 1949 and HPV-DNA was identified in 1963. It has since been demonstrated that HPV is implicated in virtually all cervical cancers.3 Specific viral subtypes implicated are HPV 16, 18, 31, 45 and others. References and Notes ^ Walboomers JM, Jacobs MV, Manos MM, et al 1999. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J. Pathol. 189 1: 12-9. doi:10.1002/SICI1096-9896199909189:112::AID-PATH4313.0.CO;2-F. PMID 10451482. ^ a b FDA Licenses New Vaccine for Prevention of Cervical Cancer, U.S. Food and Drug Administration 2006-06-08. Retrieved on 2007-12-02. ^ a b Lowy DR, Schiller JT 2006. Prophylactic human papillomavirus vaccines.. J. Clin. Invest. 116 5: 1167-73. doi:10.1172/JCI28607. PMID 16670757. Retrieved on 2007-12-01. ^ Human Papillomavirus HPV Vaccines: Q A - National Cancer Institute. Retrieved on 2008-07-18. ^ a b c d Canavan TP, Doshi NR 2000. Cervical cancer.. Am Fam Physician 61 5: 1369-76. PMID 10735343. Retrieved on 2007-12-01. ^ Nanda, Rita 2006-06-09. Cervical cancer. MedlinePlus Medical Encyclopedia. National Institutes of Health. Retrieved on 2007-12-02. ^ a b What Causes Cancer of the Cervix?. American Cancer Society 2006-11-30. Retrieved on 2007-12-02. ^ Marrazzo JM, Koutsky LA, Kiviat NB, Kuypers JM, Stine K 2001. Papanicolaou test screening and prevalence of genital human papillomavirus among women who have sex with women.. Am J Public Health 91 6: 947-52. PMID 11392939. Retrieved on 2007-12-30. ^ HPV Type-Detect. Medical Diagnostic Laboratories 2007-10-30. Retrieved on 2007-12-02. ^ Gottlieb, Nicole 2002-04-24. A Primer on HPV. Benchmarks. National Cancer Institute. Retrieved on 2007-12-02. ^ Muñoz N, Bosch FX, de Sanjosé S, Herrero R, Castellsagué X, Shah KV, Snijders PJ, Meijer CJ 2003. Epidemiologic classification of human papillomavirus types associated with cervical cancer.. N. Engl. J. Med. 348 6: 518-27. doi:10.1056/NEJMoa021641. PMID 12571259. Retrieved on 2007-12-01. ^ a b Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N 1999. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.. J. Pathol. 189 1: 12-9. doi:10.1002/SICI1096-9896199909189:112::AID-PATH4313.0.CO;2-F. PMID 10451482. Retrieved on 2007-12-01. ^ Snijders PJ, Steenbergen RD, Heideman DA, Meijer CJ 2006. HPV-mediated cervical carcinogenesis: concepts and clinical implications.. J. Pathol. 208 2: 152-64. doi:10.1002/path.1866. PMID 16362994. Retrieved on 2007-12-01. ^ Nader, Carol 2005-02-16. Expert says circumcision makes sex safer, The Age, Fairfax Media. Retrieved on 2007-12-02. ^ Rivet C 2003. Circumcision and cervical cancer. Is there a link?. Can Fam Physician 49: 1096-7. PMID 14526861. Retrieved on 2007-12-01. ^ Garcia, Agustin; Omid Hamid, Anthony El-Khoueiry 2006-07-06. Cervical Cancer. eMedicine. WebMD. Retrieved on 2007-12-02. ^ Dolinsky, Christopher 2006-07-17. Cervical Cancer: The Basics, OncoLink, Abramson Cancer Center of the University of Pennsylvania. Retrieved on 2007-12-02. ^ Erstad, Shannon 2007-01-12. Cone biopsy conization for abnormal cervical cell changes, WebMD. Retrieved on 2007-12-02. ^ Jones WB, Mercer GO, Lewis JL, Rubin SC, Hoskins WJ 1993. Early invasive carcinoma of the cervix.. Gynecol. Oncol. 51 1: 26-32. doi:10.1006/gyno.1993.1241. PMID 8244170. Retrieved on 2007-12-01. ^ Dolson, Laura 2001. Trachelectomy. Retrieved on 2007-12-02. ^ a b Burnett AF 2006. Radical trachelectomy with laparoscopic lymphadenectomy: review of oncologic and obstetrical outcomes.. Curr. Opin. Obstet. Gynecol. 18 1: 8-13. doi:10.1097/01.gco.0000192968.75190.dc. PMID 16493253. Retrieved on 2007-12-01. ^ Cibula D, Ungár L, Svárovský J, Zivný J, Freitag P 2005. Abdominal radical trachelectomy--technique and experience in Czech. Ceska Gynekol 70 2: 117-22. PMID 15918265. Retrieved on 2007-12-01. ^ Plante M, Renaud MC, Hoskins IA, Roy M 2005. Vaginal radical trachelectomy: a valuable fertility-preserving option in the management of early-stage cervical cancer. A series of 50 pregnancies and review of the literature.. Gynecol. Oncol. 98 1: 3-10. doi:10.1016/j.ygyno.2005.04.014. PMID 15936061. Retrieved on 2007-12-01. ^ Roy M, Plante M, Renaud MC, Têtu B 1996. Vaginal radical hysterectomy versus abdominal radical hysterectomy in the treatment of early-stage cervical cancer.. Gynecol. Oncol. 62 3: 336-9. doi:10.1006/gyno.1996.0245. PMID 8812529. Retrieved on 2007-12-01. ^ Dargent D, Martin X, Sacchetoni A, Mathevet P 2000. Laparoscopic vaginal radical trachelectomy: a treatment to preserve the fertility of cervical carcinoma patients.. Cancer 88 8: 1877-82. doi:10.1002/SICI1097-01422000041588:81877::AID-CNCR173.0.CO;2-W. PMID 10760765. Retrieved on 2007-12-01. ^ Schlaerth JB, Spirtos NM, Schlaerth AC 2003. Radical trachelectomy and pelvic lymphadenectomy with uterine preservation in the treatment of cervical cancer.. Am. J. Obstet. Gynecol. 188 1: 29-34. doi:10.1067/mob.2003.124. PMID 12548192. Retrieved on 2007-12-01. ^ FDA Approves First Drug Treatment for Late-Stage Cervical Cancer, U.S. Food and Drug Administration 2006-06-15. Retrieved on 2007-12-02. ^ Tiro JA, Meissner HI, Kobrin S, Chollette V 2007. What do women in the U.S. know about human papillomavirus and cervical cancer?. Cancer Epidemiol. Biomarkers Prev. 16 2: 288-94. doi:10.1158/1055-9965.EPI-06-0756. PMID 17267388. Retrieved on 2007-12-01. ^ a b What Are the Key Statistics About Cervical Cancer?. American Cancer Society 2008-03-26. Retrieved on 2008-08-19. ^ Saslow D, Runowicz CD, Solomon D, et al 2002. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA: a cancer journal for clinicians 52 6: 342-62. PMID 12469763. ^ Payne N, Chilcott J, McGoogan E. Liquid-based cytology in cervical screening: a rapid and systematic review. Health Technol Assess 2000;418. 1 ^ Willis BH, Barton P, Pearmain P, Bryan S, Hyde C. Cervical screening programmes: can automation help? Evidence from systematic reviews, an economic analysis and a simulation modelling exercise applied to the UK. Health Technol Assess 2005;913.2 ^ Naucler P, Ryd W, Törnberg S, et al 2007. Human papillomavirus and Papanicolaou tests to screen for cervical cancer. N. Engl. J. Med. 357 16: 1589-97. doi:10.1056/NEJMoa073204. PMID 17942872. ^ EU approves cervical cancer jab, BBC 2006-09-22. Retrieved on 2007-12-02. ^ GSK's HPV Vaccine 100% Effective For Four Years, Data Show, Medical News Today, MediLexicon International Ltd 2006-02-27. Retrieved on 2007-12-02. ^ Cancer jab 'stops 75% of deaths', BBC 2006-09-04. Retrieved on 2007-12-02. ^ McNeil C 2006. Who invented the VLP cervical cancer vaccines?. J. Natl. Cancer Inst. 98 7: 433. doi:10.1093/jnci/djj144. PMID 16595773. Retrieved on 2007-12-01. ^ Cornelis J.A. Hogewoning, Maaike C.G. Bleeker, et al. 2003. Condom use Promotes the Regression of Cervical Intraepithelial Neoplasia and Clearance of HPV: Randomized Clinical Trial. International Journal of Cancer 107: 811-816. doi:10.1002/ijc.11474. PMID 14566832. ^ Semen 'may fuel cervical cancer', BBC 2006-08-31. Retrieved on 2007-12-02. ^ Semen can worsen cervical cancer, Medical Research Council UK. Retrieved on 2007-12-02. ^ Cervical Cancer. Cervical Cancer: Cancers of the Female Reproductive System: Merck Manual Home ion. Merck Manual Home ion. Retrieved on 2007-03-24. ^ Committee on Practice Bulletins-Gynecology 2002. ACOG practice bulletin. Diagnosis and treatment of cervical carcinomas, number 35, May 2002. Obstetrics and gynecology 99 5 Pt 1: 855-67. PMID 11978302. ^ Cervical Cancer. Cervical Cancer: Pathology, Symptoms and Signs, Diagnosis, Prognosis and Treatment. Armenian Health Network, Health.am. ^ Cervical cancer statistics and prognosis. Cancer Research UK. Retrieved on 2007-03-24. ^ World Health Organization February 2006. Fact sheet No. 297: Cancer. Retrieved on 2007-12-01. ^ NCCC National Cervical Cancer Coalition. Retrieved on 2008-07-01. ^ Menczer J 2003. The low incidence of cervical cancer in Jewish women: has the puzzle finally been solved? PDF. Isr. Med. Assoc. J. 5 2: 120-3. PMID 12674663. Retrieved on 2007-12-01. ^ Heins Jr, HC; EJ Dennis, HR Pratt-Thomas 1958-10-01. The possible role of smegma in carcinoma of the cervix.. American Journal of Obstetrics Gynecology 76 4: 726-33. PMID 13583012. Retrieved on 2007-11-23. Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, Zahaf T, Innis B, Naud P, De Carvalho NS, Roteli-Martins CM, Teixeira J, Blatter MM, Korn AP, Quint W, Dubin G 2004. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial.. Lancet 364 9447: 1757-65. doi:10.1016/S0140-67360417398-4. PMID 15541448. Retrieved on 2007-12-01. Peto, J; C Gilham, O Fletcher, FE Matthews 2004-07-17. The cervical cancer epidemic that screening has prevented in the UK.. Lancet 364 9430: 249-56. doi:10.1016/S0140-67360416674-9. PMID 15262102. Retrieved on 2007-11-23. External links Cervical cancer at the Open Directory Project Cervical cancer at the Yahoo! Directory v d e Tumors: urogenital neoplasia - genital neoplasia C51-C63/D25-29, 179-187/218-222 Female Ovaries Surface epithelial-stromal tumor, Luteoma, Meigs syndrome, Krukenberg tumor, Teratoma, Clear cell adenocarcinoma, Endometrioid tumor, Fibroma Fallopian tube Primary fallopian tube cancer, Adenomatoid tumor Uterus Uterus Uterine sarcoma, Leiomyosarcoma Endometrium Endometrioid tumor Cervix SCC, Cervical intraepithelial neoplasia Vagina Vagina SCC, Botryoid rhabdomyosarcoma, Adenocarcinoma/Clear cell adenocarcinoma Vulva Vulva Papillary hidradenoma, Extramammary Paget's disease Male Testicles Seminoma - Spermatocytic seminoma - Endodermal sinus tumor yolk sac tumor - Embryonal tumor - Choriocarcinoma - Teratoma - Leydig cell tumor - Sertoli cell tumor Prostate Prostate - Transitional cell carcinoma - Prostatic intraepithelial neoplasia Penis Penis Extramammary Paget's disease Male/female Sex cord-stromal tumour Sertoli-Leydig cell tumour, Thecoma, Granulosa cell tumour - Germ cell tumor - Gonadoblastoma - Brenner tumour - Embryonal carcinoma See also noncongenital, congenital Retrieved from http://en..org/wiki/Cervical_cancer Categories: Sexually transmitted diseases and infections | Viral diseases | Papillomavirus | Gynecological cancerHidden categories: references cleanup | All articles with statements | Articles with statements since August 2008 | Articles with statements since June 2007 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Bosanski БългарÑ?ки Dansk Deutsch Español Français Bahasa Indonesia Lietuvių Bahasa Melayu Nederlands 日本語 ‪Norsk bokmÃ¥l‬ ‪Norsk nynorsk‬ Polski Português Simple English SlovenÅ¡Ä?ina Suomi Tiếng Việt اردو 粵語 ä¸æ–‡ This page was last modified on 11 September 2008, at 22:13
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Effects of MonaVie Active on Antioxidant Capacity in Humans
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So many of us do not eat a balanced diet, get enough sleep, have too much stress, or are impacted with toxins and pollutants. Drinking 2 ounces of MonaVie twice a day will help your body detoxify as well as build your immune system. Its the smartest thing you can do for yourself, so start today. Buying MonaVie through our company guarantees you support 7 days a week and, if you would like to share MonaVie with your family and friends we will guide you from start to finish.
1. Click on Enroll Now (30 - 55% off retail price)
2. Pay $39 for your Wholesale ID number.
3. NO minimum order required.
4. MonaVie is delivered to your door in 3 to 5 days.