WJ CO World Journal of

Clinical Oncology
Submit a Manuscript: http://www.wjgnet.com/esps/ World J Clin Oncol 2014 October 10; 5(4): 744-752
Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx ISSN 2218-4333 (online)
DOI: 10.5306/wjco.v5.i4.744 © 2014 Baishideng Publishing Group Inc. All rights reserved.

TOPIC HIGHLIGHT

WJCO 5th Anniversary Special Issues (3): Cervical cancer

Update on prevention and screening of cervical cancer

Shaniqua L McGraw, Jeanne M Ferrante

Shaniqua L McGraw, Rutgers-Robert Wood Johnson Medical This article provides an update of the preventative
School, Department of Family Medicine and Community Health, and screening methods for cervical cancer, mainly HPV
Somerset, New Jersey 08873, United States vaccination, screening with Pap smear cytology, and
Jeanne M Ferrante, Department of Family Medicine and Com- HPV testing. It also provides a discussion of the new-
munity Health, Rutgers-Robert Wood Johnson Medical School,
est United States 2012 guidelines for cervical cancer
Cancer Institute of New Jersey, New Brunswick, New Jersey
screening, which changed the age to begin and end
08903, United States
Author contributions: McGraw SL performed the research, screening and lengthened the screening intervals.
drafted the article, and approved the final version to be published;
Ferrante JM conceived and designed the research, performed © 2014 Baishideng Publishing Group Inc. All rights reserved.
research, critically revised the article, and approved the final ver-
sion to be published. Key words: Cervical cancer; Cancer screening; Pap
Correspondence to: Jeanne M Ferrante, MD, MPH, Depart- smear; Human papillomavirus; Papillomavirus vaccines
ment of Family Medicine and Community Health, Rutgers-Rob-
ert Wood Johnson Medical School, Somerset, New Jersey 08873, Core tip: Screening is the best method to prevent cervi-
United States. jeanne.ferrante@rutgers.edu cal cancer. Screening strategies should weigh the bene-
Telephone: +1-732-7433222 Fax: +1-732-7433395
fits and risks of screening to avoid discovery and need-
Received: December 28, 2013 Revised: April 11, 2014
Accepted: May 13, 2014
less treatment of transient human papillomavirus (HPV)
Published online: October 10, 2014 infections. Current United States guidelines recommend
Pap smear screening with conventional or liquid-based
method no frequent than every 3 years, or every 5
years in women greater than age of 30 if done in con-
junction with HPV testing. Screening is not recommend
Abstract in females younger than 21 years, regardless of age at
Cervical cancer is the third most common cause of initiation of sex. In this population, options for preven-
cancer in women in the world. During the past few tion include HPV vaccination and decreasing other risk
decades tremendous strides have been made toward factors associated with HPV infection.
decreasing the incidence and mortality of cervical can-
cer with the implementation of various prevention and
screening strategies. The causative agent linked to McGraw SL, Ferrante JM. Update on prevention and screen-
cervical cancer development and its precursors is the ing of cervical cancer. World J Clin Oncol 2014; 5(4): 744-752
human papillomavirus (HPV). Prevention and screening Available from: URL: http://www.wjgnet.com/2218-4333/full/
measures for cervical cancer are paramount because v5/i4/744.htm DOI: http://dx.doi.org/10.5306/wjco.v5.i4.744
the ability to identify and treat the illness at its pre-
mature stage often disrupts the process of neoplasia.
Cervical carcinogenesis can be the result of infections
from multiple high-risk HPV types that act synergisti- INTRODUCTION
cally. This imposes a level of complexity to identifying
and vaccinating against the actual causative agent. The World Health Organization estimates that yearly,
Additionally, most HPV infections spontaneously clear. about 530000 women worldwide are identified with cer-
Therefore, screening strategies should optimally weigh vical cancer and 275000 women die from the disease[1].
the benefits and risks of screening to avoid the discov- Cervical cancer is heralded as being the third most com-
ery and needless treatment of transient HPV infections. mon cause of cancer among women in the world and

WJCO|www.wjgnet.com 744 October 10, 2014|Volume 5|Issue 4|

who develops cervical cancer is considered to have AIDS. and advancement to invasive cervical types 31 and 45 detected in the developing world[8]. carcinoma in situ. chlamydia. These lesions have a 30% probability of pro- nations. Zambia and Cameroon[9-12]. and (4) the largest cause of mortality in women due to cancer in squamous cell carcinoma[8]. There are cancer will be responsible for the death of 474000 wom. HPV negative cervical cancer is extremely rare. of other sexually transmitted infections [e. (2) low grade squamous intraepithelial CERVICAL CANCER PREVENTION WITH lesions (LSILS). 1). both current and past.5]. HPV 18 with the genital skin and condom use is associated with reduced cervical cancer risk[19].19]. HPV 16 is the most crease in mortality caused by cervical cancer in the Unit.e. Prevention and screening of cervical cancer the second most common form of cancer in women in sions (HSIL). condom use is mostly causes adenocarcinoma. High-grade cervical observed during the past few decades.. Other Infection with HPV is the main causative agent in cervical sexual and reproductive risk factors associated with cancer. 58. Another potential way to prevent cervical cancer is the WJCO|www. herpes simplex can exist in pre-invasive and invasive cervical cancer[6]. greater vaginal deliveries). persistent infection and the type that is most likely to ed States from 1955 to 1992. including light dysplasia/cervical intraepi- thelial neoplasia (CIN) 1 in addition to HPV associated HPV VACCINATION cell changes. sexual activity at an early age (≤ 18 years). using condoms. The latest estimation of the number of genotypes HPV infection and cervical cancer include: initiation of of HPV was 200 with 18 genotypes that are directly relat.. Uganda. there is greater than average presence of sub. In fact. 56. with HPV clear on its own within 1-2 years[15].wjgnet. counseling for tobacco cessation. and 82. There cancer from squamous intraepithelial lesions[19]. is also a prominent presence of HPV 58 associated with cervical cancer is one of the acquired immunodeficiency pre-invasive lesions in women in various countries. High-grade There has been a large decline in the incidence and cervical intraepithelial lesions that are classified as CIN death rate of cervical cancer in industrialized countries 2 have a 40% chance of regression. severe dysplasia. in- This imposes a level of complexity in identifying which creases the risk of squamous cell cervical carcinoma. The acquisition of HPV is most dependent on contact which mostly causes squamous cell carcinoma. 33. While high-risk HPV day and number of years smoked[19]. The most carcinogenic HPV genotype is HPV 16. (3) high-grade squamous intraepithelial le. but it has been found. 59. This prominent risk increases with higher number HPV infection and cervical cancer of sexual partners of a woman or her partner[17-19]. one is the actual causative agent. 2014|Volume 5|Issue 4| . a cancer that is less fre- only 70% effective in averting the transmission of HPV quently found but more aggressive.com 745 October 10. a person with HIV cluding Thailand. Cervical cancer is responsible for 2. and carcinoma in situ/CIN 3. 45.and middle-income countries (LMICs)[3]. delaying initiation that act synergistically[14]. Each year this initial decline progress to CIN 3. The fifteen HPV types that have first full-term pregnancy (< 18 years). McGraw SL et al . in. it is expected that cervical risk factor for development of cervical cancer. multiple risk factors that have been connected with the en annually with over 95% of these deaths anticipated to acquisition of HPV infection and cervical cancer (Table occur in low. and invasive cervical in death caused by cervical cancer has been sustained at cancer. high parity (4 or a strong oncogenic potential include HPV 16. HPV acquisition is most dependent on genital con- tact. and decreasing compasses the biological behavior of cervical squamous number of sexual partners may prevent HPV infection intraepithelial lesions (SILS)[8]. gression to invasive cervical cancer[16]. 52. 73. These high. It has been found that greater than one HPV type human immunodeficiency virus (HIV). Infection with HIV 16 and 18 are accountable for around 90% of all cervical is strongly associated with incidence and persistence of cancer[7]. The use of tobacco. However. syndrome (AIDS)-defining illness. encompassing moderate dysplasia/CIN the developing world[2]. a rate of a 3% decrease in the incidence of cervical can. 2][18. This unfortunately. 18.g. In sum- esis may arise from infections with many high-risk types mary. partitions abnormal squamous epithelial cells into four categories: (1) atypical squamous cells of undermined sig- nificance (ASCUS). industrialized nations the age-adjusted incidence of cervi- cal cancer is 10 out of 100000 per year. In HPV DNA during the progression to cancer. 31. Similarly. Almost 90% of infections most developing countries. however in devel. in the United Kingdom there has been a lieved to be due to an artifact caused by limitations in the 70% decline in the mortality caused by cervical cancer current detection methods or perhaps due to the loss of recorded in 2008 than was reported 30 years prior[2]. resulting from the since there is remaining contact with genital skin that is endocervical glandular[13]. earlier age at ed to cervical cancer[4. HPV infection. and a history risk HPV typess account for 95% of all cervical cancer. An example of this is illustrated by the 70% de. cervical carcinogen- not covered by the surface of the condom[17]. oral contraceptives for longer than 5 years. However. intraepithelial lesions that do not regress are categorized has not been mirrored by a similar decline in developing as CIN 3. 68. use of combined hormonal 35. Risk factors for cervical cancer oping nations the incidence of the disease can be as high Sexually transmitted infection with HPV is the strongest as 40 out of 100000. with various genotypes and the risk rises with quantity of cigarettes smoked per depending on geographical regions. i. This form of cervical cancer is be- cer[2]. The classification system and help to reduce the risk of cervical cancer. By 2030. 51. 39. The Bethesda classification en- of sexual intercourse.

It has been mar. for the deter. Therefore. and recently. In the developing world there is a 16 and 18 in addition to HPV 6 and 11.wjgnet. ported most frequently in correlation to administration While it is known that males represent a reservoir for fe- WJCO|www. rather than preventing an infection currently approved in over 100 countries. vaccinated to obtain heard immunity. international vaccination keted as having the ability to prevent genital warts as well programs may have to change according to their country’ as cervical cancer when given in three vaccinations. Estimations have been and Drug Administration (FDA) approved in 2006. the non-routine vaccination of Gardasil in boys age nine There are a cluster of symptoms that have been re. are it prevents cancer. All of this po- by HPV. age 19 to 26 years[24]. There is a belief that men play a pivotal role dasil. Gar.15. ecchymosis (17%). McGraw SL et al . However. the HPV bivalent conservatives in the US have described the drug as “the vaccine targeting HPV 16 and 18 was approved[22]. schools report having started sexual intercourse prior cine has the capability of preventing infection with HPV to 13 years of age[26]. However. This fact is even is difficult to discern and will not be apparent for many reflected in the lack of attention given to administering years. as evidenced by its higher reduction in exci. and the vaccine has greatest efficacy in tion and subsequent cervical carcinogenesis. and it is targeted much variation in the prevalence of virginity and the age for use in females 9-26 years of age[20]. Cer. Advocates for the vaccine estimate that approximately to protective against HPV-16 and 18 infections and its as. This level of im- cination[6. munity will be hard to reach in light of the fact that many In 2008. HIV infection Routine HPV vaccination of girls is recommended Smoking by the Centers for Disease Control and Prevention’s Ad- Younger age at first sexual intercourse visory Committee on Immunization Practices (ACIP) at Greater number of sexual partners Oral contraceptives use greater than 5 yr 11 to 12 years of age with catch-up vaccinations at 13 to Having 4 or greater full-term pregnancies 26 years of age[25] (Table 2). Interestingly. a second vaccine. 1 to 2.10. cine is depicted that it is free or cheaply available and that The two HPV vaccines. However. the American Can- History of sexual transmitted diseases cer Society has not found enough research evidence to recommend for or against routine vaccination of females HIV: Human immunodeficiency virus. there has been a limited warts caused by HPV 6. The acquisition of immunity of the entire population or rence of genital warts in males age 9-26 years[6]. Cervarix also seems to Advocates for the HPV vaccination also believe that have higher cross-protection against other nonvaccine herd immunity will only authentically be obtained when HPV types. 2014|Volume 5|Issue 4| . HPV vaccines to boys and men in United States newspa- vealed with longer-term evaluations of women that were pers[29].4 years post vaccination[2. and cervical cancer[6]. and stinence from pre-marital sexual intercourse via what they 6[23]. precancerous lesions. parents that are in favor of the vaccine. Studies show that there are vidual trials. the efficacy of Cervarix in protecting against still realist barriers in place as it pertains to the cost of cervical cytologic abnormalities in HPV-naïve women is the vaccine as well as the stigma that is attached to it[27]. Short to herd immunity has been met by a great deal of challeng- medium clinical studies show the capability of Gardasil es. and 74[19]. In their indi. Gardasil also has the capabil- ity to convey protection against vulvar.13]. Positive strides have been made with regards to vaccinated in countries with population-based registries boys and men immunization when the ACIP approved that can track HPV associated cervical lesions[8]. which women marry. fainting (15%). 1 to 2. policy[28]. The Food girls who haven’t initiated sex[26]. Cervical cancer risk factors [17-19] These side effects have been reported most commonly in Genital Infection with high risk human papillomavirus younger than older girls[24]. aged 10-15 years. that is sexually transmitted[25]. to 18 years for the purpose of preventing genital warts[29]. the intention to vaccinate with HPV is greatest when the vac- cerous lesions for 6. a recombinant quadrivalent HPV vaccine. 70%-80% of girls that are pre-pubertal are required to be sociated precancerous lesions for up to 5 years post vac. Researchers believe that the differences will be re. slightly higher than Gardasil[19]. and 6[21]. Cervarix.20] . months 0. vaginal cancer Barriers to implementation of HPV vaccine and intraepithelial neoplasia. there is the existence of a gender-inclusive vaccination sional treatments for CIN 2/3 disease compared to Gar. made that only 7% of students in United States high dasil. Young women are the targeted group because immunological response is greatest in girls use of HPV vaccination to prevent high risk HPV infec. clinically amount of clinical trials that have been carried out on significant differences in efficacy of Gardasil vs Cervarix boys as it pertains to HPV vaccinations. and its efficacy in decreasing incidence of genital as carriers of HPV. This vac.8.com 746 October 10. at s conditions and traditions[27]. promiscuity vaccine” and have imposed their fears that varix is indicated for use in females aged 10 to 25 years inoculating preteen girls will disrupt their message of ab- when given in three vaccinations at months 0. Prevention and screening of cervical cancer Table 1 Cervical cancer risk factors of the HPV vaccines including pain where injected (78%). and swelling (14%). Cervarix is effective against anogenital warts caused have called the “disinhibition effects”[28]. Gardasil and Cervarix. litical rhetoric has resulted in a shift in public opinion of Short to medium clinical studies show Cervarix conveys the vaccine and resulted in a decline in the percentages of protection against HPV-16/18 and its associated precan. 11.

and 6 mo of either HPV2 or HPV4 Males age 11-12 yr Routine vaccination with HPV4 with 3 doses at 0. these populations soning. and the bivalent vaccine targets HPV 16 and 18. If just the 3rd dose is late. The 2nd and 3rd dose should be separated by 3 mo. ever. some argue that to declare that the vaccine averted have benefited from community-based awareness raising the occurrence of cervical lesions after only a few years of programs. are placed in a small glass vial that contains preserving ymptomatic invasive cervical cancer. HPV2: Bivalent human papillomavirus vaccine (Cervarix). The Females United tality in certain sub-populations. There has been much debate with regards to which discovery and needless treatment of fleeting HPV infec. McGraw SL et al . The segment of the United States popu- from acquisition of HPV infection and the first incidence lation at highest risk for cervical cancer is Hispanic and of a pre-invasive cervical lesion[22].g. there are other genotypes of HPV that are prevalent in other geographical regions. their prevalence of cervical cancer[35]. Prevention and screening of cervical cancer Table 2 Recommendations for human papillomavirus vaccination by the Advisory Committee on Immunization Practices Population Recommendation for HPV vaccination Females 11-12 yr of age Routine vaccination with 3 doses at 0. Groups of the were only conducted over a three-year timeline[21]. vaginal pain. Current evidence indicates that no clini- tion and its resultant benign lesions. and a higher risk of maternity com- plications such as preterm delivery after treatment[33. some question the cervical cancer still produces much morbidity and mor- true effectiveness of the HPV vaccine. Fortunately. how. uninsured. it takes approximately five to seven years and lesbians[24]. the cells are obtained from the neck of the The ultimate objective of cervical cancer screening is to cervix. 1-2. However. including (USPSTF) considers both of these methods to be of mental stress. if it happens. HPV4: Quadrivalent human papillomavirus vaccine (Gar- dasil). include: women who are less educated. or homeless. tological test (Pap smear) to find pre-invasive cervical versial because there is no proof that it is cost-effective[29]. but instead of being spread on a glass slide. is at least 25-30 years[22. appropriate age groups at the recommended interval[37]. However. physical discomfort incurred from extra substantial net benefit when they are administered in the diagnostic and treatment measures (e. HPV vaccination in boys is contro. while avoiding the fluid. infection). Consequently. 1-2. bleeding. to reason that programs similar to the ones implemented munity is the presence of serotypes that are not targeted on Hispanic and African-American women should be ap- by the two HPV vaccines[31.wjgnet. It is then practical Another factor that concerns the international com.. inadequate dose of HPV vaccine Insufficient receipt of HPV vaccine due to shorter than the recommended dosing interval should be re-administered Females or males with HPV vaccination does not need to be restarted. Minimum time between the 2nd and 3rd vaccine doses is 3 mo. population that participate least frequently in Pap smear the average time from carcinogenic HPV infection to inva. Although the Pap test has proven to be a greatly effec- WJCO|www. liquid-based cytology. plied to the various groups of the population where the lent vaccine prevents infection from HPV 16. In the liquid-based cytol- CERVICAL CANCER SCREENING ogy method. As a result of this rea. sive cervical cancer. ogy[36]. of the vaccine in young girls continue. which have successfully resulted in a decline in follow-up has the potential to be misleading. The 2nd dose should be administered as quick as possible if delayed interrupted vaccine schedule after the 1st dose. 18. and 6 mo. The United States Preventive Services Task Force sociated with discovering these fleeting lesions. to Unilaterally Reduce Endo/Ectocervical Disease (FU. For example.com 747 October 10. In the United States. it should be given as soon as possible HPV: Human papillomavirus vaccine. Since the majority cally important differences in sensitivity or specificity ex- of HPV infections and many CIN 1 and CIN 2 cases ists when comparing liquid-based and conventional cytol- are transient. Furthermore. migrant workers who face language barriers. form is superior. the quadriva. lesions and early stage cancer has drastically reduced the While the controversy over the cost-effectiveness of the incidence and death from cervical cancer in the United vaccine in males as well as the debate surrounding the use States and other industrialized nations [34]. In the conventional method cells are obtained from the neck of the cervix and then the cells are spread on a glass slide. Can be initiated as young as age 9 and be given up to age 26 Female or males with Minimum time between 1st and 2nd vaccine doses is 1 mo.32]. male HPV infections. their lack of compliance with Pap smear screening. 2014|Volume 5|Issue 4| .30]. approximately one-half of cervical cancer is diagnosed TURE) trials that validated the effectiveness of the vaccine in women who were never screened. and 6 mo of either HPV2 or HPV4.34]. older. a daunting Cervical cytology tests question is imposed on the effectiveness of the current There are two forms of Pap smears. conventional and vaccines in these other regions. they find high-grade cancer precursor lesions and early as. HPV testing The systemic screening with the Papanicolaou cy. 1-2. African American women. 6 and women are at greater risk to having cervical cancer due to 11. Can be initiated as early as age 9 and be given up to age 26 Females 13-26 yr of age Catch up immunization with 3 doses at 0. there is a large margin for harm that is as.

LMICs pursue a high risk. 2014|Volume 5|Issue 4| . This is due to greater ization that has the capacity to amplify the DNA signal understanding of the pathological development of cervi- in the assays of the 13 HPV high-risk types[14]. and At the present time HPV DNA testing has the high- the American Society of Clinical Pathology (ASCP) all est sensitivity. In these societies. The rea- a viable alternative to the Pap smear[41.49]. The HPV cal cancer and the discovery of the HPV DNA test and test should be performed only in women age 30 years HPV vaccines that have occurred in the last decade. These differ from previous recommenda- by numerous operational factors that inhibit quality. The previous guide- screening and treatment. McGraw SL et al . in. as they may need more frequent screenings. The HPV test is a solution hybrid- and caused higher rate of harms. Women before the age of 21 years screening and later post-diagnosis therapy. is probably untrue.05 per forms with HPV DNA testing. or were exposed in utero to jority of these LMICs do not have the current capacity diethylstilbestrol[50]. it has slightly CANCER SCREENING reduced specificity for CIN2 and CIN3 when compared In the United States. Their previous guidelines physician providers and has been extensively studied as recommended screening be done every 2 years. testing in women under the age of 30 can lead to un- The American Cancer Society (ACS).48. dicted lifetime risk of cervical cancer mortality (0. however screening women every 2 years benefit of same-visit benefit of triage by VIA-based increases the risk of colposcopies by 40% compared with screening[43-45]. On March 14. there has recently been a shift in the with cytology. A method of son behind this change in the guidelines is because 2-3 screening that is gaining increasing popularity in LMICs year screening of women before age 30 carry similar pre- is the combination of VIA-based “see-and-treat” plat. Prevention and screening of cervical cancer tive tool for screening in countries that have the capacity ongoing development of low-cost. irrespective of the age when recall and referral systems. mild or borderline abnormal Pap results. tions most notably in when to begin screening and the cluding the follow-up challenges of multiple visits for screening intervals. The higher understanding of the correlation between HPV and cervical cancer led to the develop- ment of molecular tests for HPV with greater sensitivity CURRENT GUIDELINES FOR CERVICAL (approximately 90 percent)[39]. since a negative HPV DNA test has Task Force (USPSTF) developed an updated systematic the potential to assure women that their Pap smear result review of cervical cancer screening. and prevalence of transient infection and a low prevalence of many of the organizations that develop screening guide- underlying high-grade lesions[37]. The currently available DNA test detects way that screening for cervical cancer is being conducted only the high-risk HPV types. inefficient should not have Pap smears. of Obstetrics and Gynecologist (ACOG) issued their updated guidelines for cervical cancer screening shortly Visual inspection with acetic acid thereafter in November 2012[50]. partnered with updated ACS/ASCCP/ASCP and ACOG guidelines[51. Therefore. for Colposcopy and Cervical Pathology (ASCCP). American Society needed evaluation and overtreatment[37]. However. intercourse[37. Con- or more because women less than 30 years have a high sequently. rapid molecular-assay to implement it to the majority of its population. who confounds faced by women in their countries. This screening method. A viable alternative to the Pap test should start 3 years following the initiation of sexual has been developed due its low cost and ability to “see. as it pertains with a lack of critical resources for health in general to cervical cancer screening. The consensus of rec- Low-and-middle-income countries (LMICs) are faced ommendations made by these organizations.47] . and has greater reproduc- with recognition that yearly screening was unnecessary ibility than cytology. In women with jointly produce a new cervical cancer screening guideline. whereas treatment for a positive HPV The ACS/ASCCP/ASCP group[33] and the UPSTF[36] re- DNA test may begin quicker in these women due to the leased their updated guidelines. The guidelines are not for women that are at initiatives for women. The visual inspection with acetic acid (VIA). are immunocompromised. the United States Preventive Services test may be better. to sustain cytology-based cervical cancer prevention Table 3 presents the current guidelines for specific programs[41].52] cryotherapy-based treatment of VIA-positive lesions is have increased the time between Pap smears to 3 years in a testing method that has been readily mastered by non. the Pap test is hindered age groups. are for the general popula- and often an even larger deficit for preventative health tion only. inadequate resources for they initiated sexual activity[37.51]. 2012. and competing priorities in the lines by the ACS in 2002 and 2003 stated that Pap smears healthcare systems[41]. females between ages 21 to 29.wjgnet. one technologies for HPV that may function optimally in the problem with the test is its high rate of false positive field[46. known as screening intervals in two of the age classifications. HPV DNA lines now agree on the screening recommendations[27. Hence. To combat this.42]. which can additionally be used with Pap tasked expert panels within the past five years to review smears (co-testing) for optimizing diagnosis of high- the available evidence on cervical cancer screening and grade cervical intraepithelial neoplasia[39]. The American Congress high sensitivity of this test[40]. given that they have the 1000 women). a Pap-plus-HPV At the same time.48. There has been a call for lengthening the and-treat” in one visit. The ma.com 748 October 10. screening options that work within the various societal including women with a history of cervical cancer. screening guidelines have evolved rapidly.49]. cytology[38]. 3 year screening in WJCO|www. This opportunity is made possible with the screening every 3 years[49].

58]. there is a real possibil- WJCO|www. and ing studies predicting the effectiveness of the vaccine will co-testing every 5 years results in fewer colposcopies and be available[57]. over 2 to 5 years if the woman’s test shows HPV 18[59.com 749 October 10. yr intercourse. consecutive negative 70 yr of age after > 3 negative screening result and and women not at high risk tests and no abnormal tests in previous consecutive negative women not at high risk 10 yr cytology tests over the past 10 yr Women after No screening if removal of Discontinue if hysterectomy for benign Stop screening Discontinue if hysterectomy hysterectomy cervix and no prior high grade reasons and no previous high-grade done for benign reasons pre-cancer or cervical cancer CIN Women who were Same as non-immunized No vaccines recommended for use at Same as non. HPV: Human papillomavirus. The reason for this genotyping is sparse. ACOG: American Congress of Obstetricians and Gyenocologists. Current guidelines recommend the to risk ratio. With the advent of the HPV vaccine and the limitless tomy where there was just one person found with dys.50. Cytology testing only at 3-year intervals is also HPV test. and specific recommendations in the screening guidelines. The ACS/ASCCP/ASCP and ACOG recom- satisfactory in this patient population. but no whichever is earliest later than 21 yr Females age 21–29 yr Conventional Pap or liquid Conventional Pap: Annually. ing that the risk of CIN 3 approximates 10% over 1 to There are some special circumstances that require 4 years when a woman’s test is evident for HPV 16. screening possibilities that have been afforded by the plasia and none with cervical cancer[56].wjgnet. from 70 to 65 years[49. women younger than age 30 years has the optimal benefit of the HPV vaccine. USPSTF: United States Preventive Services Task Force. option is to perform the combined HPV and cytology risk HPV infection is associated with a extremely low testing again within 12 mo[49. screening same screening strategy in individuals that have received can be done every 5 years if the woman’s result on co. the vaccine as in individuals that have not had the vaccine testing with Pap smear and HPV testing are negative. Women older than 65 Stop screening if adequate Stop screening in Women ≥ 70 yr with Stop between 65 and No screening if adequate prior prior negative screening result 3 or more recent. an acceptable alternative is that studies show in women age 65 or older. However.48. new high.49]. imme- also recommend a decrease in the age that screening is diate colposcopy[49]. McGraw SL et al . Another unique growing understanding of HPV and the role that it plays circumstance that has arisen since 2006 was the advent in the evolution of cervical cancer. because it will be another decade or more before model- since co-testing increases the sensitivity of screening. 2014|Volume 5|Issue 4| .60]. every Cytology every 2 yr Conventional Pap: At least every based cytology alone every 3 2-3 yr for females ≥ 30 with 3 negative 3 yr yr cytology tests Liquid-based cytology: Liquid-based cytology: Every 2 yr. CIN: cervical intraepithelial neoplasia.56]. These recommendations absolute risk of HPV persistence and progression to are based on results found in large cohort studies show- CIN3[55. but no later than 21 the onset of vaginal of sexual activity or age 21. No vaccines recommended for immunized with HPV women this time period immunized women use at this time period ACS: American Cancer Society. Do not use HPV testing alone. The new guidelines maintain previous recommendations to not screen women that have received hysterectomies with excision of the cervix for a benign cause and who DISCUSSION AND FUTURE PERSPECTIVE do not have prior history of cervical cytology higher than ON CERVICAL CANCER PREVENTION CIN2[37. therefore. evidence for HPV 16/18 stopped. Insufficient evidence every 2-3 yr for females ≥ 30 yr with 3 If HPV testing used: Insufficient negative cytology tests evidence If HPV testing used: Every 3 yr if HPV negative and cytology negative Females age 30–65 yr HPV and Pap smear co-testing HPV and cytology co- every 5 yr or Pap smear alone testing every 3 yr every 3 yr. The guidelines also address the situation comparable cancer risk than Pap smear screening every 3 when women have a negative Pap smear but a positive years[52.53]. Prevention and screening of cervical cancer Table 3 Comparison of cervical cancer screening guidelines Population Current Guidelines Prior ACS guideline 2002/2003 Prior ACOG Prior USPSTF guideline 2003 ACS/ACOG/USPSTF 2012 guideline 2009 Females younger than Begin screening at age 21 Begin 3 yr following the onset of Begin 3 yr following Begin within 3 yr of onset 21 yr of age vaginal intercourse. The new guidelines mend genotyping of HPV 16/18 and if positive. In women 30 to 65 years of age. This recommendation has been made in part based on evidence produced by a large study of 5330 AND SCREENING screening Pap smears in women with previous hysterec.54].

EPI-04-0812] should be conducted as the primary testing method. Pimenta JM. Smith JS.2012. Junyangdikul P.1186/1471-2334-8-85] WJCO|www. Rana RK. Meijer CJ. while Pap smear lesion and cervical cancer: will a quadrivalent vaccine be necessary in Thailand? J Med Virol 2011.CO. Chapman R. 9 Sukasem C. Human papillomavirus genotype distribu- physician providers can perform it independently. The innovative strides that have made been made screened.1002/jmv. 2014|Volume 5|Issue 4| . Vaccine 2012. Individuals that are at higher risk of acquiring cer. Therefore. 2 Arbyn M. 5 Woodman CB.1% vs 2. 14: 1157-1164 [PMID: 15894666 DOI: 10. There is a huge need to continue with the in- at the present time must be met by global efforts that are novative strides that have been made to overcome the tailored to various societal confines. Pairoj W. Green J. Evidence- the dialogue in LMICs. they should continue sending model. treat the masses of women in their countries.2012.1% with just HPV testing)[59]. Berrington de González A. 8: that HPV testing followed by Pap smear caused lower re. officials in these regions are becoming more tion. Gay N. 13: 1699-1703 these regions may take a back seat to other health care [PMID: 22799391 DOI: 10. Beral V. Colin D. ferrals for colposcopy than did either alone (1.resource countries: example of India. 83: 119-126 [DOI: screening has greater specificity. 8 Clifford GM. This aid should not only be sent in the tion of HPV vaccine impact due to unmasking of non-vac- form of the monetary contributions that have been made cine types: quantification using a multi-type mathematical by vaccine manufactures. for that vision to become a reality there are with only Pap smear or 6. Cervical cancer and hormonal contraceptives: collab- outreach and program funding is needed that are targeted orative reanalysis of individual data for 16.1093/annonc/mdr015] deaths due to cervical cancer is also at the frontline of 3 Saxena U. health care barriers crippling this population. 130: 311-321 [PMID: 19901440] knowledgeable of the advantages of implementing in.wjgnet. Plummer M.0. 7: 11-22 [PMID: 17186016 DOI: 10. More research graphic region and with cervical cancer. Goodhill A. Can cervical cancer be eradicated by prophy- types that are present based on the geographical region.03. HPV testing should be 10. Chantratita W.21948] performed initially and then obtain Pap smear screen.1016/S0140-6736(07)61684-5] The call to local and governmental officials to en. Ferlay J. as well as the ever present lack of access of certain populations to adequate health care. Sauvaget C. de Sanjosé S. 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