Cervical cancer

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Cervical cancer
Classification & external resources
Histopathologic image (H&E stain) of cervical intraepithelial neoplasia.
ICD-10 C53
ICD-9 180
OMIM 603956
DiseasesDB 2278
MedlinePlus 000893
eMedicine med/324  radio/140

Cervical cancer: 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, which has made cervical cancer the focus of intense screening efforts using the Pap smear. In developed countries, the widespread use of cervical screening programs has reduced the incidence of invasive cervical cancer by 50% or more.

Treatment consists of surgery (including local excision) in early stages and chemotherapy and radiotherapy in advanced stages of the disease. An effective HPV vaccine against the two most common cancer-causing strains of HPV has recently been licensed in the U.S. (see Vaccine section, below). These two HPV strains together are responsible for approximately 70%[1][2] of all cervical cancers. Experts recommend that women combine the benefits of both programs by seeking regular Pap smear screening, even after vaccination.

Contents

[edit] 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.

[edit] Signs and symptoms

The early stages of cervical cancer may be completely asymptomatic.[3] 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,[4] and bone fractures.

[edit] Causes

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, use of the hormonal drug diethylstilbestrol (DES) and a family history of cervical cancer.[5]

[edit] 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, leading to the development of cervical intraepithelial neoplasia, leading to cancer.

Women who have many sexual partners (or who have sex with men or women who had many partners) have a greater risk.[5][6]

More than 250 types of HPV are acknowledged to exist (some sources indicate more than 200 subtypes).[7][8] 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),[9] 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.[10]

Genital warts although caused by different HPV types have no relation 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 not all women infected with HPV develop cervical cancer.[11] Use of condoms 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.

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.[12] However, in men with low-risk sexual behaviour and monogamous female partners, circumcision makes no difference to the risk of cervical cancer.[13]

[edit] Diagnosis

[edit] 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.

[edit] 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:[14][15]

Non-carcinoma malignancies which can rarely occur in the cervix include

  • IVA - invades mucosa of bladder or rectum and/or extends beyond true pelvis
  • IVB - distant metastasis

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.

[edit] 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

[edit] 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.[16]

If a cone biopsy does not produce clear margins,[17] one more possible treatment option for patients who want to preserve their fertility is a trachelectomy.[18] 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,[19] 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 abdominally[20] or vaginally[21] and there are conflicting opinions as to which is better.[22] 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.[23] It is generally recommended to wait at least one year before attempting to become pregnant after surgery.[24] Recurrence in the residual cervix is very rare if the cancer has been cleared with the trachelectomy.[19]Yet, 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.[25] Combination treatment has significant risk of neutropenia, anemia, and thrombocytopenia side effects. Hycamtin is manufactured by GlaxoSmithKline.

[edit] Prevention

[edit] 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.[26] In 2006 an estimated 10,000 women in the US will be diagnosed with this type of cancer and nearly 4,000 will die from it.[27]

[edit] Screening

The widespread introduction of the Papanicolaou test, or pap smear for cervical cancer screening has been credited with dramatically reducing the incidence and mortality of cervical cancer in developed countries.[3] The pap smear suggests 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.[28] If premalignant disease or cervical cancer is detected early, it can be treated relatively noninvasively, and without impairing fertility.

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.[10] 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.

[edit] 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.[1] Gardasil is 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. Gardasil has also been approved in the EU.<[29]

GlaxoSmithKline has developed a vaccine called Cervarix™ which has been shown to be 100% effective in preventing HPV strains 16 and 18 and is 100% effective for more than four years.[30] These strains together cause about 70% of cervical cancer cases. Cervarix should be approved by year's end.[31]

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.[32]

In the Canadian provinces of Ontario, Prince Edward Island, Newfoundland and Nova Scotia, free vaccinations to protect women against HPV are slated to begin in September 2007 and will be offered to girls 11-14 in age. Similar vaccination programs are also being planned in British Columbia and Quebec.[33][34][35]

Australia has decided to fund the HPV vaccine under the National Immunisation Program commencing in the 2007 school year.[36] In the U.K. a similar free vaccination program is being considered,[37] while in the United States, many states[attribution needed] are preparing bills to handle issuing the HPV vaccine.[citation needed]

[edit] Prognosis

Prognosis depends on the stage of the cancer. 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.[38]

According to the International Federation of Gynecology and Obstetrics, survival improves when radiotherapy is combined with cisplatin-based chemotherapy.[39]

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.[40]

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.[41]

[edit] Epidemiology

Worldwide, cervical cancer is the fifth most deadly cancer in women.[42] 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.[3] 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.[3]

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.

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.[43][44]

[edit] History

Epidemiologists working in the early 20th century noted that:

  1. Cervical cancer was common in female sex workers.
  2. It was rare in nuns, except for those who had been sexually active before entering the convent. (Rigoni in 1841)
  3. It was more common in the second wives of men whose first wives had died from cervical cancer.
  4. It was rare in Jewish women.[45]
  5. 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 1958)[46] , 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.[2] Specific viral subtypes implicated are HPV 16, 18, 31 and 45.

[edit] See also

[edit] References and Notes

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ Nanda, Rita (2006-06-09). Cervical cancer. MedlinePlus Medical Encyclopedia. National Institutes of Health. Retrieved on 2007-12-02.
  5. ^ a b What Causes Cancer of the Cervix?. American Cancer Society (2006-11-30). Retrieved on 2007-12-02.
  6. ^ 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. 
  7. ^ HPV Type-Detect. Medical Diagnostic Laboratories (2007-10-30). Retrieved on 2007-12-02.
  8. ^ Gottlieb, Nicole (2002-04-24). A Primer on HPV. Benchmarks. National Cancer Institute. Retrieved on 2007-12-02.
  9. ^ 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. 
  10. ^ a b Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N (1999). "<12::AID-PATH431>3.0.CO;2-F Human papillomavirus is a necessary cause of invasive cervical cancer worldwide.". J. Pathol. 189 (1): 12–9. doi:<12::AID-PATH431>3.0.CO;2-F 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F. PMID 10451482. Retrieved on 2007-12-01. 
  11. ^ 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. 
  12. ^ Nader, Carol. "Expert says circumcision makes sex safer", The Age, Fairfax Media, 2005-02-16. Retrieved on 2007-12-02. 
  13. ^ Rivet C (2003). "Circumcision and cervical cancer. Is there a link?". Can Fam Physician 49: 1096–7. PMID 14526861. Retrieved on 2007-12-01. 
  14. ^ Garcia, Agustin; Omid Hamid, Anthony El-Khoueiry (2006-07-06). Cervical Cancer. eMedicine. WebMD. Retrieved on 2007-12-02.
  15. ^ Dolinsky, Christopher. "Cervical Cancer: The Basics", OncoLink, Abramson Cancer Center of the University of Pennsylvania, 2006-07-17. Retrieved on 2007-12-02. 
  16. ^ Erstad, Shannon. "Cone biopsy (conization) for abnormal cervical cell changes", WebMD, 2007-01-12. Retrieved on 2007-12-02. 
  17. ^ 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. 
  18. ^ Dolson, Laura (2001). Trachelectomy. Retrieved on 2007-12-02.
  19. ^ 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. 
  20. ^ 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. 
  21. ^ 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. 
  22. ^ 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. 
  23. ^ Dargent D, Martin X, Sacchetoni A, Mathevet P (2000). "<1877::AID-CNCR17>3.0.CO;2-W Laparoscopic vaginal radical trachelectomy: a treatment to preserve the fertility of cervical carcinoma patients.". Cancer 88 (8): 1877–82. PMID 10760765. Retrieved on 2007-12-01. 
  24. ^ 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. PMID 12548192. Retrieved on 2007-12-01. 
  25. ^ "FDA Approves First Drug Treatment for Late-Stage Cervical Cancer", U.S. Food and Drug Administration, 2006-06-15. Retrieved on 2007-12-02. 
  26. ^ 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. 
  27. ^ What Are the Key Statistics About Cervical Cancer?. American Cancer Society (2006-08-04). Retrieved on 2007-12-02.
  28. ^ 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. 
  29. ^ "EU approves cervical cancer jab", BBC, 2006-09-22. Retrieved on 2007-12-02. 
  30. ^ "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. 
  31. ^ "Cancer jab 'stops 75% of deaths'", BBC, 2006-09-04. Retrieved on 2007-12-02. 
  32. ^ 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. 
  33. ^ "McGuinty Government Launches Life-Saving HPV Immunization Program:", Premier of Ontario, 2007-08-02. Retrieved on 2007-12-02. 
  34. ^ "HPV Immunization Launched", Province of Nova Scotia, 2007-06-20. Retrieved on 2007-12-02. 
  35. ^ "British Columbia To Launch Program To Provide HPV Vaccine to Sixth-Grade Girls Next Fall if Approved, Official Says", Kaiser Daily Women's Health Policy, Kaiser Family Foundation, 2007-08-09. Retrieved on 2007-12-02. 
  36. ^ "Australian Government Funding Of Gardasil®", Australian Government Department of Health and Ageing, 2006-11-28. Retrieved on 2007-12-02. 
  37. ^ Cervical cancer vaccine. Cancer Research UK (2002). Retrieved on 2007-12-02.
  38. ^ Cervical Cancer. Cervical Cancer: Cancers of the Female Reproductive System: Merck Manual Home Edition. Merck Manual Home Edition. Retrieved on 2007-03-24.
  39. ^ 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. 
  40. ^ Cervical Cancer. Cervical Cancer: Pathology, Symptoms and Signs, Diagnosis, Prognosis and Treatment. Armenian Health Network, Health.am.
  41. ^ Cervical cancer statistics and prognosis. Cancer Research UK. Retrieved on 2007-03-24.
  42. ^ World Health Organization (February 2006). Fact sheet No. 297: Cancer. Retrieved on 2007-12-01.
  43. ^ "Semen 'may fuel cervical cancer'", BBC, 2006-08-31. Retrieved on 2007-12-02. 
  44. ^ "Semen can worsen cervical cancer", Medical Research Council (UK). Retrieved on 2007-12-02. 
  45. ^ Cite error: Invalid <ref> tag; no text was provided for refs named pmid12674663
  46. ^ 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. 

[edit] External links

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Pathology: Cancer, Tumors, Neoplasms, and oncology (C00-D48, 140-239)
Benign tumors Hyperplasia - Cyst - Pseudocyst - Hamartoma - Benign tumor
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Misc. Tumor suppressor genes/oncogenes - Staging/grading - Carcinogenesis - Carcinogen - Research - Paraneoplastic syndrome - List of oncology-related terms
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