Skip directly to site content Skip directly to page options Skip directly to A-Z link. Cervical Cancer. Section Navigation. Facebook Twitter LinkedIn Syndicate. Minus Related Pages. The worldwide prevalence of high-risk HPV infection is Several epidemiologic studies have clearly shown that the risk of contracting genital high-risk HPV infection and cervical cancer is influenced by sexual activity Erickson et al , ACOG An individual is at increased risk of having HPV infection if he or she has had multiple sexual partners at any time or if he or she has a partner who has had multiple sexual partners.
Having sexual activity at an early age as well as having a history of other sexually transmitted infections, genital warts, or cervical or penile cancer in an individual or sexual partner may also increase the risk of becoming infected with HPV. In addition to sexual activity, age is an important determinant of the risk of HPV infection Adam et al , Burk et al The infection is most common among sexually active young women between the age of 18 and 30 years with a sharp decline in prevalence after the age of 30 years.
Although, cervical cancer is more common in older women of 35 years and above, thus suggesting that the infection occurs at a younger age with a slow progression to cancer at an older age.
Persistence of HPV infection is commoner with the high-risk or oncogenic types and this plays an important role in the development of invasive cancer of the cervix Burd Cervical cancer arises at the transformation zone, which is the region between the squamous epithelium of the ectocervix and the columnar epithelium of the endocervix, where continuous metaplastic changes occur.
The period of greatest metaplastic activity coincides with the greatest risk of HPV infection and this occurs at puberty and the first pregnancy and subsequently declines slowly after the occurrence of menopause. In the past three to four decades, the natural history of cervical cancer has been well studied, and persistent infection of the cervix with certain types of HPV has been reported as a necessary causative factor for its occurrence Walboomers et al The link between HPV and cervical squamous cell carcinoma has become well established since the early 80s.
The magnitude of the association between HPV and squamous cell carcinoma of the cervix is higher than that for the association between smoking and lung cancer Franco About 30 HPV types that are transmitted through sexual contact and infect primarily the cervix, vagina, vulva, penis, and anus have been identified. One or more of these HPV types has been implicated in HPV is a family of closely related viruses with each designated as a type based on their nucleic acid sequencing and then numbered in the order of discovery.
More than HPV types are known to exist Burd , Unger et al with 15 types associated with cervical cancer. Genital HPV types can be grouped as high-risk oncogenic and low-risk non-oncogenic HPV types based on this association with cervical cancer and its precursor lesions.
Low-risk or non-oncogenic HPV types include types 6, 11, 42, 43, and 44 while the high-risk or oncogenic HPV types include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 Walboomers et al Low-risk subtypes are also occasionally found in cervical carcinomas.
The virus usually infects the mucocutaneous epithelium and produces viral particles in matured epithelial cells and then causes a disruption in normal cell-cycle control and the promotion of uncontrolled cell division leading to the accumulation of genetic damage Unger et al Adenocarcinomas of the cervix are also less commonly related to HPV infection and are age dependent Andersson et al Therefore, the detection of high-risk HPV is necessary but may not be enough for the development of cervical cancer.
Whether a woman will develop cervical cancer depends on several factors that act in conjunction with oncogenic HPV types in a process that leads to cervical cancer. These factors or modifiers of HPV activities include:. Immune response to HPV infection is cell-mediated and thus conditions that impair cell-mediated responses such as renal transplantation or HIV disease increase the risk of acquisition and progression of HPV [ Calore et al , Cubie et al , Torrisi et al Studies have consistently shown a higher prevalence of HPV infection and cervical cancer precursors in HIV infected women Conely et al , Harris et al , Singh et al This is a significant risk factor for high-grade cervical disease according to some studies Adam et , Brisson et al This is because the upstream regulatory region of high-risk HPV contains sequences which are similar to the responsive elements of glucocorticoid that can be induced by steroid hormones such as progesterone which is the active component of oral contraceptives and dexamethasone.
The suppression of local immune response induced by smoking and the mutagenic activity of tobacco components have been demonstrated in cervical cells and this may contribute to HPV persistence or to malignant changes in the cervix Philips et al , Villa , Yang et al It appears that smoking is the most important risk factor independent of HPV infection for high-grade cervical disease Adam et al Smoking shows little or no relationship to low-grade cervical disease Burd Having an increasing number of full-term pregnancies is a significant independent risk factor for persistent HPV infection and cervical cancer Shields et al , Juneja et al The possible mechanisms proposed for this are the increased hormone levels and impaired immune response of pregnancies Appleby In multiparous women, the transformation zone remains longer on the ectocervix and this facilitates its direct exposure to the virus and other potential cofactors Autier However, the most plausible mechanism is the local tissue damage occurring during vaginal childbirth or cellular oxidative stress with the increased likelihood of DNA damage and HPV integration Castle , Williams The natural history of cervical cancer offers unique opportunities for prevention of the disease Denny Cervical cancer screening involves testing for HPV infection and cervical cancer precursor lesions among women who have no symptoms.
When screening detects cervical pre-cancerous lesions, treatment can easily be instituted, and cancer avoided. Screening can also detect early-stage cervical cancer at a time when treatment has a high potential for cure.
Currently, primary approaches to HPV prevention include both risk reduction and development of vaccines against HPV infection.
Furthermore, the risk of contracting HPV may also be decreased with the use of latex condoms and spermicides. However, these are not totally reliable, since HPV infection may be transmitted through contact with other parts of the body, such as the external genitalia, or anus, that are not protected by a condom Burd This is a laboratory test in which cells from the cervix are tested for DNA from certain types of HPV that are known to cause cervical cancer.
These 2 screening strategies are meant to minimize unnecessary follow-up visits and invasive procedures without compromising the detection of disease. This is the concomitant cervical cytology and HPV testing. HPV testing is done if the results of a Pap smear test show certain abnormal cervical cells reflex testing. These improvements in cytologic screening through LBC, as well as the introduction of HPV DNA testing, greatly facilitate the identification of women at risk for cervical cancer.
In this approach, ASCUS patients would undergo cytology at 4 to 6-month intervals until two negative results are obtained after which the patient can be returned to routine cytologic screening. This is the usual approach in immunocompromised women such as those infected with HIV Holcomb et al If this is used, women with biopsy-confirmed Cervical Intraepithelial Neoplasia CIN are treated as per standard protocol using excision or coagulation techniques.
If biopsy is negative for CIN, patients will undergo repeat cytology at 12 months. In postmenopausal women who have ASCUS and clinical or cytologic evidence of atrophy, a 6-week course of intravaginal estrogen is recommended if there are no contraindications to estrogen use. Repeat cytology is performed after completion of the estrogen regimen and if this is negative, the test is repeated in 4 to 6 months. However, direct referral to colposcopy is recommended for women who test positive for any of the high-risk HPV types.
It is as effective as a hybrid screening strategy that uses cytology in women aged 25—29 years and co-testing in those at 30 years or older Wright et al However, HPV primary screening requires less screening frequency every 5 years. Several developed countries are now changing to HPV primary screening Huh et al , Leinonen et al , Ronco et al However, the development of rapid molecular methods for the detection of HPV DNA is a milestone in cervical cancer screening in these low-resource settings as these may make the test more feasible in the future and reduce the huge infrastructural requirements Catarino et al One of the major prevention strategies for cervical cancer is the vaccination against HPV infection among adolescents prior to their first sexual exposure ACOG These proteins then self-assemble into VLPs which are highly immunogenic.
In addition, the quadrivalent vaccine also protects against HPV types 6 and 11 which cause anogenital warts. Both vaccines are more effective if administered prior to exposure to HPV and thus, it is preferable to administer them before first sexual activity. Some countries have started to vaccinate boys as the vaccination prevents genital cancers in males as well as females, and the quadrivalent vaccine also prevents genital warts in males and females.
These vaccines may provide some cross-protection against other less common HPV types which cause invasive cervical cancer. Recently, a nonavalent vaccine against HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58, which has shown a better impact compared to the bivalent and quadrivalent vaccine, has been approved by the US Food and Drug Administration FDA and is now commercially available Capra et al At present, vaccination against HPV is not recommended as a replacement for cervical cancer screening and in countries where the vaccine is introduced, cervical screenings still need to be developed or further strengthened Okunade et al b.
However, in most developing countries, there is still a generally low level of awareness of the existence and availability of these HPV vaccines Okunade et al b compared to the developed countries with well-organized cervical cancer screening and HPV vaccination programs.
Several other barriers to accessing these vaccines that exist in most resource-constraint countries are the prohibitive cost which is out of the reach of the poor, the poor vaccine delivery efforts, ineffective health system capabilities, inaccessibility to medical care, low awareness and knowledge of HPV and cervical cancer, and failure to recognize cervical cancer as a major health concern Agida et al , Ezenwa et al , Okunade et al b, Perlman et al Other recommended preventive interventions against HPV infections that are appropriate for both boys and girls are education about safe sexual practices including delayed onset of sexual activity; promotion and provision of condoms for those already engaged in sexual activity; male circumcision; and warnings about tobacco smoking.
There are currently no approved therapeutic vaccines against HPV in humans. However, there are many recent studies that have generated promising vaccine candidates tested in clinical trials Vici , Yang , Kim et al Despite the success of these vaccine candidates, there still remains the concern that conventional expression methods when fully developed might result in very expensive products Giorgi et al , Rybicki that will be inaccessible to the resource-constraint countries who have the highest incidences of cervical cancer.
Molecular and epidemiologic studies have solidified the association between high-risk strains of genital HPV and squamous cell carcinoma of the cervix. The incidence of cervical cancer and its associated mortality have declined in recent years, largely due to the widespread implementation of screening programs. Screening for cervical cancer remains an important public health and economic concern throughout the world. Large-scale studies to evaluate management options for women with abnormal Pap smear results have been conducted and these studies highlighted the potential utilization of HPV DNA testing in the management of women with ASCUS Pap smear results.
The author acknowledges the mentorship provided by Prof. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.
National Center for Biotechnology Information , U. Doctors may also do an HPV test the same time they do a pap test. Vaccination against HPV is advised for females ages 9 to 26 for prevention of HPV infection, cervical cancer, as well as genital warts.
Gardasil is one such vaccine, and it guards against the two most common high-risk types of HPV, strain 16 and These two strains are responsible for 70 percent of cervical cancers. It also guards against strain 6 and 1, which cause 90 percent of genital warts. Because men can carry HPV, they should also talk to their doctors about being vaccinated. According to the CDC, preteen boys and girls should be vaccinated at age 11 or They get the vaccine in a series of three shots over an eight-month period.
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