How Successful are Pap Smears?

How successful are pap smears in detecting cervical and uterine cancers?

George Nicholas Papanicolaou established the Pap smear in the 18th century when he became intrigued by the guinea pigs vaginal smears as he was studying them. He quickly began to start his research on the female reproductive system, most specifically the different cytology slides he could obtain. His stake in the field was his book published in 1943, “Diagnosis of Uterine Cancer by Vaginal Smear.” It covered topics like physiological changes of a menstrual cycle, the hormones incorporated, and vaginal smears that led to his classifications of disease and malignancies. This jump started the screening for cervical cancer and can attest to a significant decline in cases of cervical cancer. Later, he published another book specific to just distinguishing between healthy and diseased tissue throughout the entire body. These two publications were just two of the four he finished in his life on top of awards and honorary degrees. (Tan, 2015)

Papanicolaou was certainly a huge help in the advancement of cytology reporting. Since then, we have been able to learn and understand more about pap smears, cervical cancer and the role pap smears plays in diagnosing them. Although both cancers begin in the same area, the uterus; we can differentiate them by their pathophysiology’s. The question really stands, how successful are pap smears in detecting these cancers? This can be argued on a few bases, but sticking to the facts we can find out how successful they are, how they can be preventive, and what to expect if a woman does find herself diagnosed. Several factors can be taken into account such as the pathogenesis, level of disease, the manifestations, precipitating factors, and several more. Uterine and Cervical cancers both come with their own etiologies, epidemiology’s and prognosis.

There are a few different ways to screen for cervical cancer, and this will look directly into the Pap smear procedure. The Pap smear allows for a better look into the cells in the cervix, the opening of the uterus. The test is looking for cancerous and abnormal cells that could lead to cancerous outcomes. In the test an obstetrician- gynecologist will scrape away a portion of cervix cells. The use of a speculum helps the doctor keep the walls of the cervix open to have a clear view and retrieve a good sample. The specimen will then be tested in a controlled laboratory setting where a technician will observe for abnormalities. An official cytology report will be sent to the doctor and then given back to the patient for further counsel if needed. Results will be abnormal or negative (normal). Several sources believe the Pap smear to be very accurate in the screening of cervical cancer. It also is a very preventive measure to take, as long as the patient is compliant with the doctor’s guidelines. By detecting cervical cancer early, treatment can begin to decrease the risk of spreading and growth of the tumors. Pap smears have been estimated to reduce cervical cancer rates and mortality by 80%. (Weber, 2017) In comparison, up to 80% of women diagnosed with invasive cervical cancer have not received a pap smear in the past 5 years. (Stöppler)

CIN or, cervical intraepithelial neoplasia is a precancerous condition of abnormal cell growth on the cervix. Intraepithelial means that the abnormal cells are growing on the surface or the epithelial tissue of the cervix. Neoplasia is referring to the growth of new cells. Signs and symptoms can be obvious but can also resemble several conditions that females could encounter. These symptoms can include abnormal vaginal bleeding, bleeding after sexual intercourse, pelvic pain, discharge, and pain during sexual intercourse. (Stöppler) It is recommended that women start getting pap smears at the age or 21. This is most important if you are HIV positive or have a weakened immune system. (Weber, 2017)  These screenings should continue from ages 21 to 29 with cytology alone every 3 years. From ages 30-65, women should continue cytology screening every three years and add HPV testing. After 65 no screening is necessary as long past screenings are normal and no high risk is present. (Boardman, 2018)

Over the years professionals have found it difficult to all be on the same page about reporting. Some levels of abnormal results can include atypia, mild, moderate, severe dysplasia, and carcinoma in situ. The creation of the Bethesda System has given one reporting system for all health care professionals. In 1988 the National Cancer Institute held a conference for the creation of this system, it was then re-evaluated in 2001. There are four major classifications that make it easier for this universal system to work. “ASC-US: This abbreviation stands for atypical squamous cells of undetermined significance. LSIL: This abbreviation stands for low-grade squamous intraepithelial lesion. Under the old system of classification, this category was called CIN grade I. HSIL: This abbreviation stands for high-grade squamous intraepithelial lesion. Under the old system of classification, this category was called CIN grade II, CIN grade III, or CIS. ASC-H: This means atypical cells are present and HSIL cannot be excluded.” (Stöppler)

CIN cases are most always caused by infection with oncogenic types of HPV or, Human Papillomavirus.  There are 12 known types of high risk HPV, which are the most prevalent associations with cervical cancer. Cervical cancer results from a genital infection with HPV, a known human carcinogen. Because most HPV infections are transient or, passing in and out of existence in a patient, it causes only temporary changes in cervical cells. (National Cancer Institute, 2014)  About 90% of HPV infections clear on their own within months to years with no sequelae. (Boardman, 2108) This makes it difficult to catch the HPV infection and in turn cervical cancer. Too frequent of screenings might be problematic for several reasons. One being that treating these abnormalities thinking it was HPV but that went away anyways would cause unnecessary stress on the patient. Also, putting strain on the cervix several times in any period of time can weaken the tissue and could ultimately affect the woman’s fertility. Interestingly enough, it can take up to 20 years for a persistent infection with a high risk HPV to become cancerous. (National Cancer Institute, 2014) Low risk HPV infections rarely or almost never cause cervical cancer. (Boardman, 2018) However if lesions are found and not treated, they are more than likely to turn into cervical cancer. (National Cancer Institute, 2014)

There are different levels of cervical cancer that decipher the progression on epithelial tissue. CIN grade 1 is low grade neoplasia involves around one-third of the thickness of the epithelium. CIN 2 refers to the abnormal changes in about one to two-thirds of the layer. CIN 3 is the most severe affecting over two-thirds of the epithelium. 5% of HPV infected patients will acquire CIN grade 2 or 3 lesions with three years of infection. Only 20% of CIN 3 lesions progress to invasive cervical cancer within 5 years. Only 40% of CIN 3 lesions progress to invasive cervical cancer within 30 years.

Genetics can also play a role in a woman’s development of cervical cancer; genetic connection holds fewer than only 1% of cervical cancers. “Women who have an affected first degree biological relative have a two fold relative risk of developing a cervical tumor compared with women who have a nonbiologic first degree relative with a cervical tumor.” Some specific genetic factors have been shown to be in association. The tumor necrosis factor is involved with cell apoptosis and a high incidence of cervical cancer. Polymorphisms, another gene dealing with apoptosis, have been linked to the increased rate of HPV and in turn, cervical cancer.

Cervical cancer is the leading cause of cancer related morbidity in developing countries, but is very uncommon in the United States. “Since 2004 rates have decreased by 2.1% per year in women younger than 50 years and by 3.1 per year in women 50 years of age and older. ACS reports 12,170 new cases of cervical cancer would be diagnosed in 2012.” Age related demographics from 2004-2006 were highest among women from 50-79. But cervical cancer is possible to be present in any sexually active woman. In terms of race, cervical cancer rates per 100,000 women in the US from 2005-2009 are across the board: Hispanic 11.8, African American 9.8, American Indian/ Alaska Native 8.1, White 8.0 and Asian/ Pacific Islander 7.2. Internationally, 500,000 women are diagnosed every year.

Prognosis for cervical cancer is very good, especially when caught early. 5 year survival rates: Stage 1 greater than 90%, Stage 2 60-80%, Stage 3 approximately 50%, and stage 4 less than 30%. Treatment for this type of cancer is usually dependent on age, fertility or pregnancy plans. One procedure, LEEP, the loop electrosurgical excision procedure carries an electrical current through a wire to remove abnormal tissue. Cryotherapy freezes the abnormal tissue. Laser therapy uses a beam of light to remove or even destroy the cells. Conization can also be used with a knife and laser. (Boardman, 2018) In severe cases removal of the uterus, hysterectomy is sometimes necessary. Radiation, chemotherapy and surgery can sometimes be performed in other extreme cases.

However like any screening test there is always a risk of inaccuracy in false negatives and false positives. (National Cancer Institute, 2014) In some cases a pap smear can be faulty and must be reported in an official capacity. Some examples of this could be “drying artifact’ or “excessive blood.” The person reading the smear could feel these are factors that affect the reading. Inflammation can also be a problem in a Pap smear reading. Inflammation can be from infection or irritation. (Stöppler)

Uterine cancer is defined as the any invasive neoplasm of the uterine corpus and is the most common pelvic gynecological malignancy in the United States. Uterine cancer can also be labeled endometrial cancer. The most common type of uterine cancer specifically is endometrioid adenocarcinomas. (Chiang, 2017) It is believed to have two forms; type 1 or estrogen dependent and type 2, which is estrogen independent. (Holman 2012)

Uterine cancer can start in small areas or “a diffuse multifocal pattern.” Health care professionals can usually diagnose this type of cancer by the spreading pattern of the tumor. Usually the tumor will grow from the original location. This can tell the doctor how far along the cancer is. Later tumor growth is seen through myometrial invasion and movement towards the cervix. The cancer itself can take four different routes to spread outside the uterus. Direct or local extends beyond the uterus. Lymphatic, referring to exposure to the pelvic, para-aortic, and sometimes the lymph nodes. Hematologic goes further reaching the lungs, liver, and bone metastatically. Lastly, “peritoneal/ transtubular spread results in intraperitoneal implants.

Staging of Uterine cancer, like most cancers, will depend on the amount of growth and spreading of the tumors. Clinical stage 1, which is the most common for patients, is strict to the uterus. Stage 2 involves a large amount of the cervix. Stage 3 “ vaginal extension, adnexal mass, and/or suspicious retroperitoneal lymphadenopathy.” Stage 4 accesses the bowel and bladder and some other metastases around the body.

Although pap smears are prominent for cervical cancer findings, it is not as helpful in uterine cancer. According to my findings, there are actually no screening regimens for asymptomatic women. The only screening mentioned is a transvaginal ultrasound, which “determines the thickness in postmenopausal women.” In the suspicion of abnormalities, biopsies can be taken. Uterine cancer usually includes both surgery and radiotherapy. Other treatments follow a hormone regimen. Other forms can use estrogen replacement therapy and Tamoxifen, which is usually used for breast cancer but can be used on endometrium tissue as well. (Holman 2012) Because of the early representation of the cancer, treatment is usually successful and most do not progress past stage 1. Recurrences can happen and usually do within 3 years of the original diagnoses, which occurs in half of patients. (Holman 2012)(Uterine Cancer)

Symptoms of uterine cancer can range from genital discharge, pain, weight loss, and change in bladder or bowel movements. However, postmenopausal bleeding is said to diagnose up to 90% of endometrial cancers. Another clinical finding would be glandular cells from a pap smear on a postmenopausal woman. Some risk factors are obesity, nulliparity, and late menopause. Diabetes and hypertension are also conditions that. Less than 5% of this cancer is actually diagnosed when the woman is asymptomatic can increase the risk of uterine cancer. (Uterine Cancer) Most of the patients diagnosed with uterine cancer are obese, which can affect estrogen levels. (Holman 2012)

Over 50,000 cases of uterine cancer are diagnosed each year, leading up to 10,000 deaths per year. In women alone, it leads to 4% of deaths related to cancer. 70-75% of cases are diagnosed at stage 1. In 2009, the survival rate for uterine cancer was 83.1%. (Chiang, 2017) A large majority of the population diagnosed are postmenopausal and ages 50-65, average age of 61. White women have the largest risk of uterine cancer in the United States compared to African American, Asian and Hispanic women. However, African American women have a larger rate of death. Interestingly, those women living in Asia or Africa have a much smaller rate of uterine cancer than Asian and African American women in the United States. Smoking actually has been shown to decrease your chance of endometrial cancer. The use of contraceptive pills has also been said to be a protective measure for women. (Holman 2012)

In conclusion, Pap Smears can be resourceful ways of detecting cervical cancer but not at large uterine cancers. Pap smears are a great screening method for obstetrician- gynecologists and their patients to catch and prevent cervical cancer. By detecting cervical cancer early, prognosis is very good and very likely in most cases. These quick diagnoses from pap smears and other sources has made cervical cancer a very uncommon cancer related death for women in the United States. Unfortunately for developing countries, lack of medical resources and research has made discovering cervical cancer difficult and fatal. With the Bethesda System doctors from all over can classify cervical cancer the same way. Pap smears are very accurate, but like any screening procedure there is always the risk of false negatives or false positives.

Although Pap smears haven’t been shown totally reliable to detect uterine cancer, there are several other methods to find uterine cancer. The most obvious can be the presence of postmenopausal bleeding in women, which diagnoses most of the cases. Transvaginal ultra sound can be used to determine the state of the woman’s uterine tissue. These and a few others have been said to be more reliable than Pap smears. Counterpart to ruling out Pap smear findings, one source does tell that if glandular cells are present than it might be uterine cancer. Like cervical cancer, uterine cancer is most always found in early stages or stage 1 to be exact. This early detection makes it only 4% of cancer related deaths in women.

In doing my research it was clear to me that Pap smears are in fact helpful in detecting cervical cancer but not as much in uterine cancer. I only found one source that mentioned findings from a Pap smear for uterine cancer. This was entirely interesting to me because they are in very similar areas of the woman’s reproductive system. In doing more research, it makes sense that a pap smear rarely diagnoses uterine cancer because it starts inside the uterus. The cervix being much lower and away from the uterus makes it easier to obtain cells and much more reliable. Finding cervical cancer can be much more direct and easily obtained. Getting to the uterus safely is much more difficult.

In further research I believe it would be interesting to look further into minimally invasive ways to detect uterine cancer. Another topic is using the any findings from a Pap smear in detecting cervical cancer to relate to prevention of uterine cancer. Lastly, the result of cervical and uterine cancer on future pregnancy or on currently pregnant women.

Works Cited

“Uterine Cancer.” Uterine Cancer, www.csh.org.tw/dr.tcj/educartion/f/web/Uterine%20Cancer/index.htm.

Boardman, Cecelia. “Cervical Cancer.” Practice Essentials, Background, Pathophysiology, 26 Jan. 2018, emedicine.medscape.com/article/253513-overview.

Chiang, Jing. “Uterine Cancer.” Background, History of the Procedure, Epidemiology, 6 Dec. 2017, emedicine.medscape.com/article/258148-overviewuterine cancer.

Holman , Laura. “The Epidemiology of Endometrial Cancer.” The Epidemiology of Endometrial Cancer, 2012, www.glowm.com/section_view/heading/The%20Epidemiology%20of%20Endometrial%20Cancer/item/236.

Stöppler, Melissa Conrad. “Pap Smear: Facts About the Procedure, Pain & Guidelines.”MedicineNet, www.medicinenet.com/pap_smear/article.htm#what_is_a_pap_smear_procedure.

Tan, Siang Yong, and Yvonne Tatsumura. “George Papanicolaou (1883–1962): Discoverer of the Pap Smear.” Singapore Medical Journal, Singapore Medical Association, Oct. 2015, www.ncbi.nlm.nih.gov/pmc/articles/PMC4613936/.

Weber, Michael. “Pap Smear (Pap Test): Reasons, Procedure, & Results.” Healthline, Healthline Media, 13 Mar. 2017, www.healthline.com/health/pap-smear.