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Cervical cancer

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Cervical cancer is malignant neoplasm 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 strains of HPV that cause the most cervical cancer has been licensed in the U.S. and the EU. These two HPV strains together are currently responsible for approximately 70%[2][3] of all cervical cancers. Since the vaccine only covers some high-risk types, women should seek regular Pap smear screening, even after vaccination.[4]

Signs and symptoms

The early stages of cervical cancer may be completely asymptomatic. 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 faeces from the vagina,[5] and bone fractures.

Risk Factors

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.[6] There is a possible genetic risk associated with HLA-B7.

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 partner. 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.[7] However, in men with low-risk sexual behaviour and monogamous female partners, circumcision makes no difference to the risk of cervical cancer.[8]

Diagnosis

Visual inspection to detect precancer or cancer

Visual inspection of the cervix, using acetic acid or Lugol’s iodine to highlight precancerous lesions so they can be viewed with the “naked eye”, shifts the identification of precancer from the laboratory to the clinic. Such procedures eliminate the need for laboratories and transport of specimens, require very little equipment and provide women with immediate test results. A range of medical professionals—doctors, nurses, or professional midwives—can effectively perform the procedure, provided they receive adequate training and supervision. As a screening test, VIA performs equal to or better than cervical cytology in accurately identifying pre-cancerous lesions.[9] This has been demonstrated in various studies where trained physicians and mid level providers correctly identified between 45% and 79% of women at high risk of developing cervical cancer.[10] By comparison, the sensitivity of cytology has been shown to be between 47 and 62%.It should be noted, however, that cytology provides higher specificity than VIA. Like cytology, one of the limitations of VIA is that results are highly dependant on the accuracy of an individual’s interpretation. This means that initial training and on-going quality control are of paramount importance.

VIA can offer significant advantages over Pap in low-resource settings, particularly in terms of increased screening coverage, improved follow up care and overall program quality. Due to the need for fewer specialized personnel and less infrastructure, training, and equipment, with VIA public health systems can offer cervical cancer screening in more remote (and less equipped) health care settings and can achieve higher coverage. Furthermore, providers can share the results of VIA with patients immediately, making it possible to screen and treat women during the same visit. This helps ensure that follow up care can be provided on the spot and reduces the number of women who may miss out on treatment because they are not able to return to the clinic at another time. In a “screen and treat” project in Peru, for example, only 9% of women who screened positive failed to receive treatment in the single-visit approach, compared with 44% of women who were lost to treatment using a multi-visit model.[11]

VIA has successfully been paired with cryotherapy, a relatively simple and inexpensive method of treating cervical lesions that can be performed by primary care physicians and mid-level providers.[12]

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 a dilute 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.

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.[13]

If a cone biopsy does not produce clear margins,[14] one more possible treatment option for patients who want to preserve their fertility is a trachelectomy.[15] 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,[16] 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[17] or vaginally[18] and there are conflicting opinions as to which is better.[19] 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.[20] It is generally recommended to wait at least one year before attempting to become pregnant after surgery.[21] Recurrence in the residual cervix is very rare if the cancer has been cleared with the trachelectomy.[16] 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.[22] Combination treatment has significant risk of neutropenia, anemia, and thrombocytopenia side effects. Hycamtin is manufactured by GlaxoSmithKline.

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 outcomes may be partly based on the state of treatment five years ago when the women studied were first diagnosed.[23]

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.[24]

According to the International Federation of Gynecology and Obstetrics, survival improves when radiotherapy is combined with cisplatin-based chemotherapy.[25]

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.[26]

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.[27] About 1,000 women per year die of cervical cancer in the UK.

Regular two-yearly Pap tests can reduce the incidence of cervical cancer by up to 90% in Australia, and save 1,200 Australian women dying from the disease each year.[28]

Epidemiology

Worldwide, cervical cancer is the fifth most deadly cancer in women.[29] It affects about 16 per 100,000 women per year and kills about 9 per 100,000 per year.[30]

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. 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. The incidence of new cases of cervical cancer in the United States was 7 per 100,000 women in 2004.[31]

In the United Kingdom, the incidence is 9.1/100,000 per year (2005), similar to the rest of Northern Europe, and mortality is 3.1/100,000 per year (2006) (Cancer Research UK Cervical cancer statistics for the UK)[32]. 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.

In Canada, an estimated 1,300 women will be diagnosed with cervical cancer in 2008 and 380 will die.[33]

In Australia, there were 734 cases of cervical cancer (2005).The number of women diagnosed with cervical cancer has dropped on average by 4.5% each year since organised screening began in 1991 (1991-2005).[34].

Worldwide it is estimated that there are 473,000 cases of cervical cancer, and 253,500 deaths per year.[35]

References and Notes

  1. ↑ 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. <12::AID-PATH431>3.0.CO;2-F doi:10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F. PMID 10451482. 
  2. ↑ "FDA Licenses New Vaccine for Prevention of Cervical Cancer", U.S. Food and Drug Administration, 2006-06-08. Retrieved on 2007-12-02. 
  3. ↑ 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. 
  4. ↑ Human Papillomavirus (HPV) Vaccines: Q & A - National Cancer Institute. Retrieved on 2008-07-18.
  5. ↑ Nanda, Rita (2006-06-09). Cervical cancer. MedlinePlus Medical Encyclopedia. National Institutes of Health. Retrieved on 2007-12-02.
  6. ↑ What Causes Cancer of the Cervix?. American Cancer Society (2006-11-30). Retrieved on 2007-12-02.
  7. ↑ Nader, Carol. "Expert says circumcision makes sex safer", The Age, Fairfax Media, 2005-02-16. Retrieved on 2007-12-02. 
  8. ↑ Rivet C (2003). "Circumcision and cervical cancer. Is there a link?". Can Fam Physician 49: 1096–7. PMID 14526861. Retrieved on 2007-12-01. 
  9. ↑ Sherris J. et al. Evidence-Based, Alternative Cervical Cancer Screening Approaches in Low-Resource Settings. International Perspectives on Sexual and Reproductive Health. Volume 35, Number 3, September 2009
  10. ↑ Sankaranarayanan R et al. A critical assessment of screening methods for cervical neoplasia. International Journal of Gynecology and Obstetrics. 2005;89 Suppl 2:S4–S12.
  11. ↑ Luciani S, Winkler J. Cervical Cancer prevention in Peru: Lessons learned from the TATI demonstration project. Washington, DC: Pan American Health Organization; 2006.
  12. ↑ Gage JC, Ferreccio C, Gonzales M, Arroyo R, Huivin M, Robles SC. Follow-up care of women with an abnormal cytology in a low-resource setting. Cancer Detection and Prevention. 2003;27(6):466–471.
  13. ↑ Erstad, Shannon. "Cone biopsy (conization) for abnormal cervical cell changes", WebMD, 2007-01-12. Retrieved on 2007-12-02. 
  14. ↑ 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. 
  15. ↑ Dolson, Laura (2001). Trachelectomy. Retrieved on 2007-12-02.
  16. ↑ 16.0 16.1 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. 
  17. ↑ 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. 
  18. ↑ 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. 
  19. ↑ 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. 
  20. ↑ 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. <1877::AID-CNCR17>3.0.CO;2-W doi:10.1002/(SICI)1097-0142(20000415)88:8<1877::AID-CNCR17>3.0.CO;2-W. PMID 10760765. Retrieved on 2007-12-01. 
  21. ↑ 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. 
  22. ↑ "FDA Approves First Drug Treatment for Late-Stage Cervical Cancer", U.S. Food and Drug Administration, 2006-06-15. Retrieved on 2007-12-02. 
  23. ↑ What Are the Key Statistics About Cervical Cancer?. American Cancer Society (2006-08-04). Retrieved on 2007-12-02.
  24. ↑ Cervical Cancer. Cervical Cancer: Cancers of the Female Reproductive System: Merck Manual Home Edition. Merck Manual Home Edition. Retrieved on 2007-03-24.
  25. ↑ 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. 
  26. ↑ Cervical Cancer. Cervical Cancer: Pathology, Symptoms and Signs, Diagnosis, Prognosis and Treatment. Armenian Health Network, Health.am.
  27. ↑ Cervical cancer statistics and prognosis. Cancer Research UK. Retrieved on 2007-03-24.
  28. ↑ http://www.papscreen.org.au/
  29. ↑ World Health Organization (February 2006). Fact sheet No. 297: Cancer. Retrieved on 2007-12-01.
  30. ↑ GLOBOCAN 2002 database: summary table by cancer
  31. ↑ SEER cancer statistics
  32. ↑ http://info.cancerresearchuk.org/cancerstats/types/cervix/mortality/
  33. ↑ Noni MacDonald, Matthew B. Stanbrook, and Paul C. Hébert (September 9, 2008). "Human papillomavirus vaccine risk and reality" (in French). CMAJ 179 (6): 503, 505. doi:10.1503/cmaj.081238. PMID 18762616. Retrieved on 2008-11-17. 
  34. ↑ http://www.papscreen.org.au/browse.asp?ContainerID=c15
  35. ↑ NCCC National Cervical Cancer Coalition. Retrieved on 2008-07-01.

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