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Cervical cancer
Classification and external resources
Image:Cervical intraepithelial neoplasia (5) CIN3.jpg
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
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 International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors The uterus also has a round leiomyoma up higher. A leiomyoma (plural is 'leiomyomata' is a Benign Smooth muscle Neoplasm that is not Premalignant.

Cervical cancer is malignant cancer of the cervix uteri or cervical area. Malignant (from the Latin roots mal- = "bad" and -genus = "born" is a medical term used to describe a severe and progressively worsening disease Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled The cervix (from Latin "neck" is the lower narrow portion of the Uterus where it joins with the top end of the Vagina. It may present with vaginal bleeding but symptoms may be absent until the cancer is in its advanced stages. Vaginal bleeding refers to bleeding in females that is either a physiologic response during the non-conceptional Menstrual cycle or caused by hormonal or organic problems of Treatment consists of surgery (including local excision) in early stages and chemotherapy and radiotherapy in advanced stages of the disease. Surgery (from the χειρουργική cheirourgikē, via chirurgiae meaning "hand work" is a medical specialty that uses operative manual and instrumental Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. Radiation therapy (or radiotherapy) is the medical use of Ionizing radiation as part of Cancer treatment to control Malignant

Pap smear screening can identify potentially precancerous changes. The Papanicolaou test (also called Pap smear, Pap test, cervical smear, or smear test) is a screening test used in Gynecology 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. A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been [1] HPV vaccine effective against the two most common cancer-causing strains of HPV has been licensed in the U. Human papillomavirus (HPV vaccine is a Vaccine that targets certain strains of Human papillomavirus associated with the development of Cervical S. and the EU. These two HPV strains together are currently responsible for approximately 70%[2][3] of all cervical cancers. Experts recommend that women combine the benefits of both programs by seeking regular Pap smear screening, even after vaccination.


Contents

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. A carcinoma is any Malignant Cancer that arises from epithelial cells. In Anatomy, squamous epithelium (from Latin squama, "scale" is an Epithelium characterised by its most superficial layer consisting The term head and neck cancer refers to a group of biologically similar cancers originating from the upper aerodigestive tract including the Lip, Oral cavity ( Anal cancer is a type of Cancer which arises from the Anus, the distal orifice of the Gastrointestinal tract. All three of these diseases may be associated with human papillomavirus infection. A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been An infection is the detrimental Colonization of a host Organism by a foreign Species.

Signs and symptoms

The early stages of cervical cancer may be completely asymptomatic. [4] Vaginal bleeding, contact bleeding or (rarely) a vaginal mass may indicate the presence of malignancy. Vaginal bleeding refers to bleeding in females that is either a physiologic response during the non-conceptional Menstrual cycle or caused by hormonal or organic problems of 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. Metastasis ( Greek: displacement μετά=next + στάσις=placement, plural metastases) sometimes abbreviated mets, In Vertebrates such as Mammals the abdomen (belly constitutes the part of the body between the Thorax (chest and Pelvis. lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive

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,[5] 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. A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been 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. An oncovirus is a Virus associated with Cancer. Oncoviruses come in two different forms viruses with a DNA Genome, such as Adenovirus Cervical intraepithelial neoplasia ( CIN) also known as cervical dysplasia is the potentially Premalignant transformation and abnormal growth ( Dysplasia

Women who have many sexual partners (or who have sex with men or women who had many partners) have a greater risk. [6][7]

More than 250 types of HPV are acknowledged to exist (some sources indicate more than 200 subtypes). [8][9] 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),[10] 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. A risk factor is a variable associated with an increased risk of Disease or Infection. [11]

Genital warts are caused by different HPV types and have no relation to cervical cancer. Genital warts (or Condyloma, Condylomata acuminata, or venereal warts) is a highly contagious Sexually transmitted

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. A sexually transmitted disease ( STD) or venereal disease ( VD) is an illness that has a significant probability of transmission between Humans [12] Use of condoms reduces, but does not always prevent transmission. A condom is a device most commonly used during Sexual intercourse. 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. In biology and medicine epithelium is a tissue composed of cells that line the cavities and surfaces of structures throughout the body The glans penis (or simply glans) is the sensitive tip of the Penis. Cleanliness is the absence of dirt including Dust, Stains bad smells and Garbage.

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. The American Cancer Society ( ACS) is the "nationwide community-based voluntary health organization dedicated to A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been Tobacco Smoking is the inhalation of smoke from burned dried or cured leaves of the Tobacco plant most often in the form of a Cigarette. Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome Hormonal contraception refers to Birth control methods that act on the hormonal system Pregnancy ( Latin graviditas) is the carrying of one or more offspring known as a Fetus or Embryo, inside the Uterus of a Female Diethylstilbestrol ( DES) is a drug, an orally active synthetic nonsteroidal Estrogen that was first synthesized in 1938 In Medicine, a family history consists of information about disorders that a patient's direct blood relatives have suffered from [6]

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. Male circumcision is the removal of some or all of the Foreskin (prepuce from the Penis. 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. [13] However, in men with low-risk sexual behaviour and monogamous female partners, circumcision makes no difference to the risk of cervical cancer. [14]

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. Screening, in medicine is a strategy used in a Population to detect a Disease in individuals without signs or Symptoms of that disease This is often done through colposcopy, a magnified visual inspection of the cervix aided by using an acetic acid (e. Colposcopy is a medical diagnostic procedure to examine an illuminated magnified view of the Cervix and the tissues of the Vagina and Vulva. Acetic acid, also known as ethanoic acid, is an organic chemical compound, giving Vinegar its sour taste g. vinegar) solution to highlight abnormal cells on the surface of the cervix. Vinegar is an acidic liquid processed from the Fermentation of Ethanol in a process that yields its key ingredient Acetic acid (also called ethanoic acid

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. The loop electrosurgical excision procedure ( LEEP) is currently one of the most commonly used approaches to treating high grade Cervical dysplasia discovered on Cervical conization ( ICD-9 code 672 CPT codes 57520(Cold Knife and 57522(Loop Excision refers to a Biopsy of the Cervix in which a cone-shaped These are carried out if the biopsy confirms severe cervical intraepithelial neoplasia. Cervical intraepithelial neoplasia ( CIN) also known as cervical dysplasia is the potentially Premalignant transformation and abnormal growth ( Dysplasia

Pathologic types

Cervical intraepithelial neoplasia, the precursor to cervical cancer, is often diagnosed on examiniation of cervical biopsies by a pathologist. Cervical intraepithelial neoplasia ( CIN) also known as cervical dysplasia is the potentially Premalignant transformation and abnormal growth ( Dysplasia Pathology (from Greek grc πάθος pathos, "fate harm" and grc -λογία -logia) is the study and Histologic subtypes of invasive cervical carcinoma include the following:[15][16]

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

Note that the FIGO stage does not incorporate lymph node involvement in contrast to the TNM staging for most other cancers. Histopathology (from the Greek histos (tissue and pathos (suffering refers to the microscopic examination of tissue in order to study the manifestations In Medicine, squamous cell carcinoma (SCC is a form of Cancer of the Carcinoma type that may occur in many different organs including the Skin Adenocarcinoma is a cancer that originates in Glandular tissue Adenosquamous carcinoma is a type of Cancer that contains two types of cells Squamous cells (thin flat cells that line certain organs and gland-like cells Small cell carcinoma is a type of Carcinoma usually associated with the Lung, though it can be associated with other topographies such as in Cervical cancer Melanoma is a Malignant Tumor of Melanocytes which are found predominantly in skin but also in the Bowel and the Eye (see Lymphoma a type of Neoplasm that originates in Lymphocytes (a type of White blood cell in the vertebrate Immune system) A Lymph node ( lɪmf noʊd is an organ consisting of many types of cells and is a part of the Lymphatic system. The TNM Classification of Malignant Tumours ( TNM) is a Cancer staging system that describes the extent of Cancer in a patient’s body

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. Cervical intraepithelial neoplasia ( CIN) also known as cervical dysplasia is the potentially Premalignant transformation and abnormal growth ( Dysplasia

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. The International Federation of Gynecology and Obstetrics, usually just FIGO as the acronym of its French name Fédération Internationale de Gynécologie et d'Obstétrique 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. Colposcopy is a medical diagnostic procedure to examine an illuminated magnified view of the Cervix and the tissues of the Vagina and Vulva. Curettage, in Surgery, is the use of a Curette to remove tissue by scraping or scooping Hysteroscopy is the inspection of the uterine cavity by Endoscopy. Endoscopy of the Urinary bladder via the Urethra is called cystoscopy Proctoscopy is a common medical procedure in which an instrument called a proctoscope (also known as a rectoscope is used to examine the Anal cavity, Rectum or An intravenous pyelogram (also known as IVP, pyelography, intravenous urogram or IVU) is a radiological procedure used to visualize X-radiation (composed of X-rays) is a form of Electromagnetic radiation. Cervical conization ( ICD-9 code 672 CPT codes 57520(Cold Knife and 57522(Loop Excision refers to a Biopsy of the Cervix in which a cone-shaped

The TNM staging system for cervical cancer is analogous to the FIGO stage. The TNM Classification of Malignant Tumours ( TNM) is a Cancer staging system that describes the extent of Cancer in a patient’s body

Treatment

Microinvasive cancer (stage IA) is usually treated by hysterectomy (removal of the whole uterus including part of the vagina). In biology and medicine epithelium is a tissue composed of cells that line the cavities and surfaces of structures throughout the body In animal tissue stroma (from Greek στρώμα meaning “bed” refers to the connective non-functional supportive framework of a biological cell, tissue Carcinoma in situ (CIS is an early form of Carcinoma defined by the absence of invasion of surrounding tissues Hydronephrosis is distention and Dilation of the Renal pelvis and calyces, usually caused by Obstruction of the free flow of Metastasis ( Greek: displacement μετά=next + στάσις=placement, plural metastases) sometimes abbreviated mets, A hysterectomy (from Greek hystera "womb" is the surgical removal of the Uterus, usually performed by a gynecologist. The vagina (from Latin, literally " Sheath " or " Scabbard " is a fibromuscular tubular tract leading from the Uterus For stage IA2, the lymph nodes are removed as well. A Lymph node ( lɪmf noʊd is an organ consisting of many types of cells and is a part of the Lymphatic system. 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. The loop electrosurgical excision procedure ( LEEP) is currently one of the most commonly used approaches to treating high grade Cervical dysplasia discovered on Cervical conization ( ICD-9 code 672 CPT codes 57520(Cold Knife and 57522(Loop Excision refers to a Biopsy of the Cervix in which a cone-shaped [17]

If a cone biopsy does not produce clear margins,[18] one more possible treatment option for patients who want to preserve their fertility is a trachelectomy. In Gynecologic oncology, trachelectomy, also cervic[[ ectomy|ectomy]], is a surgical removal of the uterine Cervix. [19] 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,[20] 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[21] or vaginally[22] and there are conflicting opinions as to which is better. [23] 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. [24] It is generally recommended to wait at least one year before attempting to become pregnant after surgery. [25] Recurrence in the residual cervix is very rare if the cancer has been cleared with the trachelectomy. [20]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. Colposcopy is a medical diagnostic procedure to examine an illuminated magnified view of the Cervix and the tissues of the Vagina and Vulva. Safe sex (also called safer sex or protected sex) is the practice of Sexual activity in a manner that reduces the risk of Infection with

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 (or radiotherapy) is the medical use of Ionizing radiation as part of Cancer treatment to control Malignant Radiation therapy is given as external beam radiotherapy to the pelvis and brachytherapy (internal radiation). Brachytherapy (from the Greek brachy, meaning "short" also known as sealed source radiotherapy or endocurietherapy, is a form of 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. Cisplatin, cisplatinum or cis -diamminedichloridoplatinum(II (CDDP is a Platinum -based Chemotherapy drug used to treat

Advanced stage tumors (IIB-IVA) are treated with radiation therapy and cisplatin-based chemotherapy. Cisplatin, cisplatinum or cis -diamminedichloridoplatinum(II (CDDP is a Platinum -based Chemotherapy drug used to treat

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. Events 763 BC - Assyrians record a Solar eclipse that will be used to fix the Chronology of Mesopotamian history Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Topotecan hydrochloride (trade name Hycamtin) is a chemotherapy agent that is a topoisomerase 1 inhibitor. Cisplatin, cisplatinum or cis -diamminedichloridoplatinum(II (CDDP is a Platinum -based Chemotherapy drug used to treat [26] Combination treatment has significant risk of neutropenia, anemia, and thrombocytopenia side effects. Neutropenia (adjective neutropenic) from Latin Prefix neutro- and Greek Suffix -πενία (deficiency is Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative Thrombocytopenia (or -paenia, or thrombopenia in short is the presence of relatively few Platelets in Blood. 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. The National Cancer Institute (NCI is part of the United States Federal government's National Institutes of Health. [27] 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. [28]

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. The Papanicolaou test (also called Pap smear, Pap test, cervical smear, or smear test) is a screening test used in Gynecology [4] 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. Cervical intraepithelial neoplasia ( CIN) also known as cervical dysplasia is the potentially Premalignant transformation and abnormal growth ( Dysplasia 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. The American Cancer Society ( ACS) is the "nationwide community-based voluntary health organization dedicated to [29] 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. A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been 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. [11] 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. Cervical intraepithelial neoplasia ( CIN) also known as cervical dysplasia is the potentially Premalignant transformation and abnormal growth ( Dysplasia A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare [30] The relative risk reduction was 41. The relative risk reduction is a measure used in Epidemiology. 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%. In Epidemiology, the absolute risk reduction is the decrease in Risk of a given activity or treatment in relation to a control activity or treatment 3. 8 patients must be treated for one to benefit (number needed to treat = 3. The number needed to treat (NNT is an epidemiological measure used in assessing the effectiveness of a health-care intervention typically a treatment with Medication 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. Human papillomavirus (HPV vaccine is a Vaccine that targets certain strains of Human papillomavirus associated with the development of Cervical Merck & Co Inc ( also known as Merck Sharp & Dohme or MSD outside the USA and Canada, is one of the largest Pharmaceutical companies Gardasil ( Merck & Co) is a Vaccine against certain types of Human papillomavirus (HPV It is now on the market after receiving approval from the US Food and Drug Administration on June 8, 2006. Events 68 - The Roman Senate accepts emperor Galba. 536 - St Silverius becomes Pope (probable Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. [2] Gardasil has also been approved in the EU. [31]

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. GlaxoSmithKline plc () is a United Kingdom -based pharmaceutical, biological and Healthcare Company. Cervarix is a Vaccine against certain types of the Human papillomavirus (HPV [32] Cervarix has been approved some places and is in approval process elsewhere. [33]

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. The National Cancer Institute (NCI is part of the United States Federal government's National Institutes of Health. The University of Rochester ( U of R UR) is a private, nonsectarian Coeducational Research University located in Rochester Georgetown University is a Jesuit Private university located in Georgetown Washington D Washington DC ( formally the District of Columbia and commonly referred to as Washington, the District, or simply D Dartmouth College ( is a private, Coeducational University located in Hanover, New Hampshire, U The University of Queensland (UQ is one of Australia's premier learning and research institutions Brisbane ( is the state capital of Queensland. Brisbane is the third most populous city in Australia and the most populous city of Queensland Both Merck & Co. and GlaxoSmithKline have licensed patents from all of these parties. [34]

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. In the United States, many states are preparing bills to handle issuing the HPV vaccine. [35]

Condoms

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. A prostaglandin is any member of a group of Lipid compounds that are derived enzymatically from Fatty acids and have important functions in the Animal body Physiological aspects Internal and external fertilization Depending on the Species, spermatozoa can fertilize A condom is a device most commonly used during Sexual intercourse. [36][37]

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. Years of potential life lost ( YPLL) or potential years of life lost ( PYLL) is an estimate of the Average years a person would have lived if 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]

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.

In the United States, it is only the 8th most common cancer of women. The United States of America —commonly referred to as the In 1998, about 12,800 women were diagnosed in the US and about 4,800 died. [4] Among gynecological cancers it ranks behind endometrial cancer and ovarian cancer. Endometrial cancer refers to several types of malignancy which arise from the Endometrium, or lining of the Uterus. Ovarian cancer is a cancerous growth arising from an Ovary. The cancer most commonly forms in the lining of the ovary (resulting in epithelial 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 Papanicolaou test (also called Pap smear, Pap test, cervical smear, or smear test) is a screening test used in Gynecology [4]

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.

History

Epidemiologists working in the early 20th century noted that:

  1. Cervical cancer was common in female sex workers. Epidemiology is the study of factors affecting the Health and Illness of populations and serves as the foundation and Logic of interventions made in the A sex worker is a person who works in the Sex industry. Sex workers may be employed as prostitutes strippers go-go dancers burlesque performers escorts dominatrices
  2. It was rare in nuns, except for those who had been sexually active before entering the convent. A Nun is a Woman who has taken special vows committing her to a religious life (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. [43]
  5. In 1935, Syverton and Berry discovered a relationship between RPV (Rabbit Papillomavirus) and skin cancer in rabbits. Rabbits are small Mammals in the family Leporidae of the order Lagomorpha, found in several parts of the world (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. This article is about smegma a secretion of mammalian genitals g. Heins et al 1958)[44] , but it wasn't until the 1970s that human papillomavirus (HPV) was identified. A human papillomavirus ( HPV) is a Papillomavirus that infects the skin and Mucous membranes of Humans Approximately 130 HPV types have been A description by electron microscopy was given earlier in 1949 and HPV-DNA was identified in 1963. An electron microscope is a type of Microscope that uses Electrons to illuminate a specimen and create an enlarged image 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.

See also

References and Notes

  1. ^ Walboomers JM, Jacobs MV, Manos MM, et al (1999). Vaginal cancer is any type of Cancer that forms in the tissues of the Vagina. "Human papillomavirus is a necessary cause of invasive cervical cancer worldwide". J. Pathol. 189 (1): 12-9. doi:10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 10451482.  
  2. ^ a b "FDA Licenses New Vaccine for Prevention of Cervical Cancer", U.S. Food and Drug Administration, 2006-06-08. Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 68 - The Roman Senate accepts emperor Galba. 536 - St Silverius becomes Pope (probable Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire  
  3. ^ a b Lowy DR, Schiller JT (2006). "Prophylactic human papillomavirus vaccines.". J. Clin. Invest. 116 (5): 1167–73. doi:10.1172/JCI28607. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16670757.  
  4. ^ a b c d Canavan TP, Doshi NR (2000). "Cervical cancer.". Am Fam Physician 61 (5): 1369–76. PMID 10735343.  
  5. ^ Nanda, Rita (2006-06-09). Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 53 - Roman Emperor Nero marries Claudia Octavia 62 - Claudia Octavia commits Cervical cancer. MedlinePlus Medical Encyclopedia. National Institutes of Health. "NIH" redirects here For other meanings of NIH see NIH (disambiguation. Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire
  6. ^ a b What Causes Cancer of the Cervix?. American Cancer Society (2006-11-30). The American Cancer Society ( ACS) is the "nationwide community-based voluntary health organization dedicated to Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 1700 - Battle of Narva — A Swedish army of 8500 men under Charles XII defeats Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire
  7. ^ 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.  
  8. ^ HPV Type-Detect. Medical Diagnostic Laboratories (2007-10-30). Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 637 - Antioch surrenders to the Muslim forces under Rashidun Caliphate after the Battle of Iron bridge. Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire
  9. ^ Gottlieb, Nicole (2002-04-24). See also 2002 (disambiguation Year 2002 ( MMII) was a Common year starting on Tuesday of the Gregorian calendar. Events 1479 BC - Thutmose III ascends to the throne of Egypt, although power effectively shifts to Hatshepsut (according to A Primer on HPV. Benchmarks. National Cancer Institute. The National Cancer Institute (NCI is part of the United States Federal government's National Institutes of Health. Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire
  10. ^ 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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12571259.  
  11. ^ 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/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 10451482.  
  12. ^ 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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16362994.  
  13. ^ Nader, Carol. "Expert says circumcision makes sex safer", The Age, Fairfax Media, 2005-02-16. Year 2005 ( MMV) was a Common year starting on Saturday (link displays full calendar of the Gregorian calendar. Events 1249 - Andrew of Longjumeau is dispatched by Louis IX of France as his ambassador to meet with the Khan of the Mongols Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire  
  14. ^ Rivet C (2003). "Circumcision and cervical cancer. Is there a link?". Can Fam Physician 49: 1096–7. PMID 14526861.  
  15. ^ Garcia, Agustin; Omid Hamid, Anthony El-Khoueiry (2006-07-06). Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 1044 - The Battle of Ménfő takes place 1189 - Richard the Lionheart is crowned King of England Cervical Cancer. eMedicine. WebMD. WebMD is a medical and wellness information service primarily known for its public Internet site which provides health information a symptom checklist pharmacy information blogs of Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire
  16. ^ Dolinsky, Christopher. "Cervical Cancer: The Basics", OncoLink, Abramson Cancer Center of the University of Pennsylvania, 2006-07-17. The University of Pennsylvania (also known as Penn) is a private University located in Philadelphia, Pennsylvania, USA. Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 180 - Twelve inhabitants of Scillium in North Africa are executed for being Christians Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire  
  17. ^ Erstad, Shannon. "Cone biopsy (conization) for abnormal cervical cell changes", WebMD, 2007-01-12. WebMD is a medical and wellness information service primarily known for its public Internet site which provides health information a symptom checklist pharmacy information blogs of Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 475 - Basiliscus becomes Byzantine Emperor, with a coronation ceremony in the Hebdomon palace in Constantinople Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire  
  18. ^ 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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 8244170.  
  19. ^ Dolson, Laura (2001). Trachelectomy. Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire
  20. ^ 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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16493253.  
  21. ^ 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.  
  22. ^ 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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15936061.  
  23. ^ 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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 8812529.  
  24. ^ 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/(SICI)1097-0142(20000415)88:8<1877::AID-CNCR17>3.0.CO;2-W. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 10760765.  
  25. ^ 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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12548192.  
  26. ^ "FDA Approves First Drug Treatment for Late-Stage Cervical Cancer", U.S. Food and Drug Administration, 2006-06-15. Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 763 BC - Assyrians record a Solar eclipse that will be used to fix the Chronology of Mesopotamian history Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire  
  27. ^ 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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17267388.  
  28. ^ What Are the Key Statistics About Cervical Cancer?. American Cancer Society (2006-08-04). The American Cancer Society ( ACS) is the "nationwide community-based voluntary health organization dedicated to Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 70 - The Destruction of the Second Temple in Jerusalem by the Romans. Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire
  29. ^ 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.  
  30. ^ 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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17942872.  
  31. ^ "EU approves cervical cancer jab", BBC, 2006-09-22. Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 66 - Emperor Nero creates the Legion I Italica. 1236 - The Lithuanians Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire  
  32. ^ "GSK's HPV Vaccine 100% Effective For Four Years, Data Show", Medical News Today, MediLexicon International Ltd, 2006-02-27. Medical News Today is a web-based outlet for medical news targeted to both physicians and the general public Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 1560 - The Treaty of Berwick, which would expel the French from Scotland, is signed by England and the Congregation Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire  
  33. ^ "Cancer jab 'stops 75% of deaths'", BBC, 2006-09-04. Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 476 - Romulus Augustus, last emperor of the Western Roman Empire, is deposed when Odoacer proclaims himself Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire  
  34. ^ McNeil C (2006). "Who invented the VLP cervical cancer vaccines?". J. Natl. Cancer Inst. 98 (7): 433. doi:10.1093/jnci/djj144. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16595773.  
  35. ^ HPV vaccine
  36. ^ "Semen 'may fuel cervical cancer'", BBC, 2006-08-31. Human papillomavirus (HPV vaccine is a Vaccine that targets certain strains of Human papillomavirus associated with the development of Cervical Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 1056 - Byzantine Empress Theodora becomes ill dying suddenly a few days later without children to succeed the Throne Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire  
  37. ^ "Semen can worsen cervical cancer", Medical Research Council (UK). The Medical Research Council (MRC is a UK organisation dedicated to "promot the balanced development of medical and related biological research Retrieved on 2007-12-02. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1409 - The University of Leipzig opens 1755 - The second Eddystone Lighthouse is destroyed by fire  
  38. ^ Cervical Cancer. Cervical Cancer: Cancers of the Female Reproductive System: Merck Manual Home Edition. Merck Manual Home Edition. Retrieved on 2007-03-24. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1401 - Mongol emperor Timur sacks Damascus. 1603 - James VI of Scotland
  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. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1401 - Mongol emperor Timur sacks Damascus. 1603 - James VI of Scotland
  42. ^ World Health Organization (February 2006). Fact sheet No. 297: Cancer. Retrieved on 2007-12-01. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 800 - Charlemagne judges the accusations against Pope Leo III in the Vatican
  43. ^ 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.  
  44. ^ 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.  

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