Late Bhagirathi Yashwatrao Pathrikar College of pharmacy (D & B pharm) pathri phulambri chh. Sambhajinagar 43111.
Over 300,000 people die from cervical cancer worldwide, making it the fourth most frequent malignancy among women. Prolonged infection with high-risk subtypes of the human papillomavirus is the cause of cervical cancer, and the E5, E6, and E7 viral oncoproteins work in tandem with host factors to initiate and sustain the malignant phenotype. The majority of cervical cancer may be prevented, and survival rates are considerably higher when the disease is detected early. It is considered a rare disease in high-income nations with well-established screening and vaccination programs. But in low- and middle-income nations, where resources are scarce, the disease kills women, who frequently have advanced, incurable sickness. Surgical procedures, chemotherapy, and/or radiation therapy are available as treatments, either separately or in combination.
Around 500,000 women worldwide are diagnosed with cervical cancer each year, making it a severe health issue. The majority of incidents take place in less developed nations without efficient screening infrastructure. Smoking, immune system dysfunction, and human papillomavirus exposure are risk factors. Although long-term treatment-related morbidity is prevalent, the majority of women with early-stage tumors can be cured. Chemo-radiotherapy should be considered the standard of care for women with locally advanced malignancies, according to the results of randomized clinical trials. However, it is still entirely unknown if this treatment is appropriate for women in less developed nations. Despite unresolved concerns regarding the morbidity of this method in comparison to definitive radiotherapy or radical surgery, many women with localized (stage IB) tumors still get various combinations of surgery and radiation therapy. Recurrent cervical cancer is still mostly unresponsive to treatment. The majority of CC patients now have far better clinical results thanks to advancements in common treatments like chemotherapy, radiation, and surgery. Nonetheless, a significant proportion of patients continue to develop locally advanced CC, with 5-year survival rates below 60%.1 The majority of women who have cervical cancer go through a protracted phase of asymptomatization before the illness manifests clinically. Consequently, early detection of aberrant cytologic alterations by routine screening may stop the development of pre-invasive to invasive illness. Women who are at risk of invasive cervical cancer can be identified, which helps doctors choose patients who need ongoing screening instead of yearly screening.2
Quality of life should be taken account in management of CC
When treating women with primary and recurrent cervical cancer, quality of life should be considered.3 The management of any cancer should include a strategy that may provide the patients with the highest possible overall quality of life (QOL), not only the treatment of the clinical illness. The WHO defines quality of life (QOL) as an individual's perception of their own place in the culture and values system in which they live, along with their own goals, limitations, standards, and concerns. This broad definition was influenced by the individual's health, cognitive state, social relationships, degree of independence, and relationship to the environment.4 To properly balance the treatment choice, however, side effects and therapy expenses must also be taken into account. Patients often think about the sum of their abilities, situations, and physical experiences rather than thinking in terms of toxicity vs efficacy. Indeed, people frequently mistake symptoms for adverse consequences. In an unscreened population, up to 5% of people will acquire cervical cancer in their lifetime.
Drugs that destroy the cancer cells may be part of further therapies. Among the options might be targeted treatment medications and chemotherapy. It is also possible to utilize radiation treatment with strong energy beams. Occasionally, low-dose chemotherapy is combined with radiation therapy. Cervical precancers can be effectively screened for and treated to lower the lifetime risk to less than 0.5%. In order to detect and treat precancers and prevent cervical cancer, it is advised that asymptomatic people undergo routine screening. Due in large part to notable differences in availability to human papillomavirus (HPV) vaccination, screening, and treatment facilities in different areas, the disease is more prevalent among women in low- and middle-income countries.5
Physiology of cervical cancer
The cervix is where cervical cancer begins, and it is an unchecked cell proliferation. In the uterus, the lowest portion that joins the vagina is called the cervix. When cells in the cervix develop improperly and begin to multiply quickly, the disease known as cervical cancer develops. The cervix grows out of control and develops into a tumor. Squamous cell carcinoma is the most prevalent kind of cervical cancer, accounting for up to 90% of cases. Although it is less frequent and more challenging to identify, adenocarcinoma is another kind of cervical cancer. Without treatment, the cells have the potential to infiltrate healthy tissue and spread to other areas of the body. Symptoms like menstrual abnormalities, Pain and, vaginal discharge can be seen. The most common gynecological cancer in poorer nations, cervical cancer ranks third globally in terms of cancer incidence.6 Following therapy for dysplasia, the incidence of cervical cancer is less than 1%, and the death rate is less than 0.5%.7 The early onset of sexual activity, certain sexual behaviors such as having many partners, having sex at a young age, not using condoms frequently, having multiple pregnancies with Chlamydia, and immunosuppression with HIV are all linked to an increased risk of HPV infection.These factors are also responsible for the disease's rising trend in developing nations. Compared to women who are HIV-negative, women with HIV are more likely to have and sustain several HPV infections, which are linked to a greater chance of developing precancerous cervical lesions.8
Role of EGFR in the development, sustenance and progression of CC.
Cervical cancer (CC) was identified as a major cause of morbidity and death in women by the subcommittee for CC management established by the Indian Council of Medical Research (ICMR) and described in the consensus document (2016). One of the main causes of cancer in women is the incidence of an increase in CC and the corresponding mortality. 9To date, about 99 percent of CC cases are caused by human papillomavirus (HPV) infection. Nonetheless, some HPV-infected people do not have CC. Upregulation of the epidermal growth factor receptor (EGFR) signaling cascade during the onset, maintenance, and development of CC is more closely associated with HPV infection. Tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAB) are therefore frequently used to target EGFR in order to cure CC. Using the Kaplan–Meier (KM) survival plot analysis for disease-free survival (DFS) and overall survival (OS), the current study examined the importance of EGFR abundance and the clinical/preclinical investigations that have already been conducted. Changes in endogenous microRNAs (miRNA) brought on by EGFR mutations during CC.The need for improved medicines and potential resistance to the current EGFR medications, such as TKIs and mABs, are also thoroughly evaluated in order to generate novel therapeutic compounds with greater efficacy.10
Metastasis: The lung, liver, bone, and colon are the most often affected areas.
Development: Cervical intraepithelial neoplasia (CIN), which can take 10–20 years to progress, is typically the precursor to cervical cancer. The transformation zone, where Squamous and glandular cells converge, is where the majority of cervical malignancies begin.
Impact of CC in relation to other cancer
The number of years lost from a woman's life can also be used to gauge the impact of cervical cancer. Approximately 26 years of life are lost for every woman who passes away from cervical cancer on average. Only testicular cancer in men (35.9 years) is lower than this, and it is significantly higher than the average number of years of life lost to breast cancer (19.2 years).11 Moreover, acquired immune deficiency syndrome is the only disease that causes women to lose more average years of life (34.5 years).12
Figure 1: Cervical cancer screening
Risk factors for cervical cancer include:
1. Human papillomavirus:
The genome of HPV, a double-stranded circular DNA virus, contains roughly 8000 base pairs.13 Two late structural proteins (L1 and L2) and six early regulatory proteins (E1, E2, E4, E5, E6, and E7) are encoded by the genome. Cervical cancer growth is tightly linked to HPV, a double-stranded circular DNA virus.14 The majority of cervical malignancies are caused by different strains of the human papillomavirus, or HPV. A frequent infection spread during intercourse is HPV. The body's immune system usually stops HPV from causing damage when it is present. However, in a tiny minority of individuals, the virus persists for years. This plays a part in the process that turns some cervical cells into cancerous ones. According to estimates, 10–15% of women carry oncogenic HPV types (low risk: 6, 11, 40, 42, 43, 44, 54, 61, 72, 81 and high risk: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 69, and 82). It is estimated that HPV16 or 18 infection accounts for 71% of the worldwide burden of invasive cervical cancer.15 Getting vaccinated against HPV infection and undergoing screening tests can lower your risk of developing cervical cancer. At least 14 high-risk HPV strains have been identified as carcinogenic out of the more than 100 varieties of HPV.16Only chronic infections with certain HPV types can result in abnormalities of cervical cells; the majority of HPV infections are self-curable and do not induce precancerous cell alterations. After many years, these abnormalities (precancerous or high grade lesions) may develop into cervical cancer if they are not treated.17
2. Sexual activity
Getting sexually active at a youthful age, or having multiple sexual mates, can increase the threat of HPV exposure.18
3. Chlamydia
Sexual intercourse can spread the common bacterial illness known as chlamydia. Although it affects people of various ages, young ladies are more likely to experience it. Even if a person with chlamydia does not exhibit any symptoms, they can still spread the infection to others through intercourse. Friendly discomfort and discharge from the penis or vagina are possible symptoms. In addition to increasing the risk of cervical cancer, chlamydia can cause pelvic inflammation and gravidity in women.
4. Oral contraceptives
Long term use of birth control pills can increase the risk of cervical cancer.
5. Obesity
Obesity can make cervical cancer screening more difficult, which can lead o a higher risk of cancer.
6. Smoking and STD
In addition to smoking, women who have a history of sexually transmitted infections, human papillomavirus (HPV) infection, and low socioeconomic level, two or more lifetime sexual partners, or immunosuppression are at risk for developing cellular abnormalities. The latter features contribute to frequent exposure to carcinogens, and their necessary presence lends credence to the theory that cervical cancer is a disease spread by sexual contact. Although nicotine is not thought to be a cause, smoking can increase a woman's risk of developing cervical cancer by reducing her immune surveillance at the cellular level.19 Additionally, smokers may exhibit behaviors that make them more vulnerable to cancerous transformation. A radical hysterectomy should be carried out with the fetus in place before 20 weeks of pregnancy; after that, it is advised to evacuate the fetus before surgery. Delaying treatment until fetal survival is guaranteed is a fair option in stage I disease for patients with a previable fetus, but it is not advised for those with more advanced disease.20 Although the delivery route is hotly contested, delivery should occur as soon as the fetus exhibits pulmonary maturity. Since there is a chance of disease recurrence at the episiotomy site and since delivering a baby via a cervix with advanced cervical cancer raises the risk of infection, obstructed labor, and hemorrhage, the majority of specialists recommend cesarean delivery.21
7. Weak immune system
Having HIV or another condition ha makes it difficult o fight off health problems can increase the risk.
8. Age
Table 1: This table gives an idea about risks of CC varying with age groups.
|
Age |
Incidence rates |
|
Age 15–19
|
Incidence rates rise sharply from this age group. |
|
Age 20–29
|
Women under 40 are diagnosed with cervical cancer at a rate of 21%. |
|
Age 30–39
|
78% of cervical cancer cases in women under 40 are diagnosed in this age group. |
|
Age 35–44
|
This is the age group with the highest number of cervical cancer diagnoses, and the average age of diagnosis is 50. |
|
Age 65 and older
|
Women over 65 are at risk for more than 20% of cervical cancer cases. However, if you've been screened regularly and had normal test results, your health care provider may advise you that you no longer need screening. |
The risk of cervical cancer varies by age, with the highest incidence rates in women between the ages of 30 and 34
Cervical cancer in India
According to GLOBOCAN 2020, cervix uteri cancer is the second leading cause of death (9.1%) and the third most common cause of death (18.3%, or 123,907 cases) in India. The age-standardized incidence rate per 100,000 people was 18, while the 5-year prevalence rate for all ages was 42.82 per 1 lakh population. Breast cancer and cervix uteri cancer were the most common cancers in women, according to the National Cancer Registry Program. 22Cervical cancers made for 6-29% of all cancers in Indian women. The Indian state of Arunachal Pradesh's Papumpare region has the highest incidence rate of cervical cancer in Asia (27.7). Most patients were diagnosed at the locally advanced stage of breast (57.0%), cervix uteri (60.0%), head and neck (66.6%), and stomach (50.8%) cancers; however, distant metastases were more prevalent in males (44.0%) and females (47.6%) with lung cancer. Most patients were diagnosed at the locally advanced stage of breast (57.0%), cervix uteri (60.0%), head and neck (66.6%), and stomach (50.8%) cancers; however, distant metastases were more prevalent in males (44.0%) and females (47.6%) with lung cancer.
Study conduct in India
According to research conducted in rural Tamil Nadu, India, with limited resources, screening acceptance was initially low even if screening programs were accessible. However, the number of women having screening increased as community awareness rose. This may be accomplished by community involvement, necessary output, and optimization of health knowledge, beliefs, and attitudes.
Figure 2: To create awareness of cervical cancer
Immunotherapy:
Utilizing the body's immune system to combat illness or infection is known as immunotherapy. Numerous illnesses, including as allergies, autoimmune diseases, and cancer, can be treated with it. Immunotherapy might include immune system stimulation, immune system suppression, and immunological system desensitization.
1. Identification of m6A-related lncRNAs
It is clinically significant to investigate the variables that influence immunotherapy results. New molecular markers and therapeutic approaches are therefore essential for the prognosis and personalized choice of the best adjuvant approach for CC.24 Numerous biological activities including mRNA metabolism depend on N6-methylandenosine (m6A), the most prevalent internal methylation modification of mammalian RNA.25 Demethylases (erasers), signal transducers (readers), and methyltransferases (writers) are all involved in controlling m6A modification.26 In order to maintain appropriate m6A levels and gene expression, m6A writers and erasers work together, contributing to the etiology of several illnesses, including cancer.27
2. A2ML1 Detection
Cervical cancer is significantly linked to A2ML1, which is seen in people with advanced disease. Using data from the TCGA database, this study demonstrated that A2ML1 is broadly expressed in cervical cancer. The hypothesis that there is a connection between A2ML1 expression and the effectiveness of immunotherapy or chemotherapy was validated using the Genomics of Drug Sensitivity in Cancer database.28 The results showed that A2ML1 is a possible biomarker for the diagnosis of cervical cancer. In addition to explaining how the immune milieu causes cervical cancer, this biomarker may be utilized to chaperone treatment.
Target Therapy
Understanding genetic abnormalities that may be used therapeutically has been a more clinically significant result of the TCGA and related molecular profiling studies. The table displays a list of chosen targets and related substances that may have therapeutic significance.
|
Table 2: Potential targets and corresponding in cervical cancer. |
|
|
Target |
Agents approved or in trials |
|
VEGF/VEGFR (VEGF; Vascular endothelial growth factor); (VEGFR; Vascular endothelial growth factor receptor) |
Bevacizumab, pazopanib, sunitinib, nintedanib, brivanib, cediranib |
|
CD274(also known as PD-L1) amplification (CD274;cluster of differentiation 274) (PD-L1; programmed death ligand 1) |
Immune checkpoint inhibitors |
|
PDCD1LG2 (also known as PD-2) amplification (PD-L2; programmed death ligand 2) |
Immune checkpoint inhibitors |
|
BCAR4 amplification/ HER2 (breast cancer anti-estrogen resistance 4)/ (HER2 human epidermal growth factor receptor |
lapatinib |
|
PARP (poly ADP ribose polymerase) |
Olaparib, veliparib |
|
HDAC ( histone deacetylase ) |
Valproic acid |
|
EGFR (epidermal growth factor receptor) |
Cetuximab, gefitinib, erlotinib |
|
mTOR (mammalian target of rapamycin |
Temsirolimus |
Cervical cancer screening
Women who do not follow up after a precancerous lesion or who have not been tested in the previous five years is at a greater risk of dying. Screenings for cervical cancer, such the Pap test, can identify alterations in cells before they develop into cancer.
Women's cervical cancer screening has reduced the disease's incidence and death rate. Sexually transmitted high-risk HPV infection, which is responsible for almost 99% of cervical malignancies, is closely linked to precancerous cervical lesions (cervical intraepithelial neoplasia) and cervical carcinomas. HPV testing and cytology (Papanicolaou test) are screening techniques that can be used separately or in combination.31 According to American Cancer Association guidelines, the Pap test, the HPV DNA test, and the preventative vaginal and cervical smear are excellent diagnostic techniques for tracking down asymptomatic women and following up with those who have had therapy for pre-invasive cervical cancer. The FIGO 2009 and 2018 staging system for cervical cancer serves as the foundation for treatment.
|
Table 3: Comparison of the 2009 and 2018 FIGO staging classifications.32 |
||
|
Stage |
FIGO 2009 staging defines |
FIGO 2018 staging defines |
|
Stage I |
Carcinoma is strictly confined to the cervix. |
Carcinoma is strictly confined to the cervix. |
|
Stage IA |
Invasion is limited to measure stromal Infiltration with a maximum depth of 5 mm - 7 mm. |
Depth less than or equal to 5mm |
|
Stage IA2 |
Measured stromal invasion more than 3mm depth and not more than 5 mm and extension |
More than 3mm and less than or equal to 5mm depth |
|
Stage IB |
Clinically visible lesions limited to the cervix or pre-clinical cancers greater than stage 1A. |
Lesion greater than 5mm depth Or stage 1A |
|
Stage IB1 |
Clinically visible tumors less than 4cm are greatest dimension. |
less than or equal to 2cm ,maximum diameter |
|
Stage IB2 |
Tumour is clinically visible, more than 4 cm in greatest dimension, parametrial involvement, but not into pelvic sidewall. |
more than 2cm and less than or equal to 4cm,maximum diameter |
|
Stage II |
Cancer extends beyond cervix though not to the pelvic sidewall or lower one 3rd of the vagina. |
Cancer extends beyond cervix though not to the pelvic sidewall or lower one 3rd of the vagina |
|
Stage IIA |
Involves upper two third of vagina. |
Involves upper two third of vagina |
|
Stage IIA1 |
Clinically visible tumour less than or equal to 4cm is greatest dimension. Its involvement is up to the upper two thirds of the vagina. |
Clinically visible tumour less than or equal to 4cm is greatest dimension. It involvement is up to the upper two thirds of the vagina. |
|
Stage IIA2 |
Clinically visible tumour greater than 4 cm in greatest dimension. Its involvement is up to the upper two thirds of the vagina. |
Clinically visible tumour greater than 4 cm in greatest dimension. Its involvement is up to the upper two thirds of the vagina. |
|
Stage IIB |
Having parametrial invasion, but not into the pelvic sidewall. |
Having parametrial invasion, into the pelvic sidewall |
|
Stage III |
Lower vagina, pelvic sidewall and ureters |
Lower vagina ,pelvic sidewall ureters, and lymph nodes |
|
Stage IIIa |
Lower 1/3rd of vagina |
Lower 1/3rd of vagina |
|
stage IIIb |
Pelvic sidewall involvement |
Pelvic sidewall involvement |
|
stage IIIC |
...... |
Involvement pelvic lymph node and Para-aortic lymph node |
|
stage IIIC1 |
...... |
Involvement pelvic lymph node |
|
stage IIIC2 |
...... |
Involvement Para-aortic lymph node |
|
Stage IV |
Carcinoma that has extended beyond the pelvis or adjacent organs |
Carcinoma that has extended beyond the pelvis or adjacent organs |
|
Stage IVa |
Adjacent pelvic organs, extension beyond pelvis or rectal/bladder invasion. |
Adjacent pelvic organs, extension beyond pelvis or rectal/bladder invasion. |
|
Stage IVb |
spread to distant organ |
spread to distant organ |
The primary cause of cancer-related mortality among women in developing nations is cervical cancer. The development of new technology has made it possible to test for and treat cervical cancer more quickly, cheaply, and sensitively.33 Cervical cancer recurrence rates range from 10% to 20% for FIGO stages Ib–IIa and from 50% to 70% for locally progressed cases (stages IIb–IVa). The severe malignant development of both locally recurrent and chronic pelvic tumors, as well as their frequently complicated anatomical topography, makes curative therapy exceedingly challenging and infrequently effective.34
Pap test
According to the American Cancer Society, women should start annual cervical cancer screening with the Pap test when they turn 18 or after they start having sex, whichever comes first. At the doctor's discretion, screening may be done less often following three consecutive negative Pap tests.35 It is not recommended to screen younger women with either the Pap or HPV tests. Every three years, women between the ages of 21 and 29 should get Pap tests. When two or more consecutive negative cytology findings are obtained in women aged 21 to 29, there is insufficient data to support a longer delay between screenings (>3 years). Only after abnormal Pap test results should the HPV test is administered at these ages. Co-testing (Pap and HPV) should be performed every five years on women aged 30 to 65. Although continuous Pap test screening every three years is permissible, this kind of screening is preferred. There is not enough data to justify prolonged test intervals in this age range following many negative tests.36Although the Pap test is a successful screening tool, it is ineffective for diagnosing cancer because cytology cannot provide crucial information about the size of the lesion and the depth of invasion. Additionally, it might be challenging to evaluate cytologic alterations brought on by cancer, which can result in misleading negative findings.37 The most recent recommendations for mass population screening preserve the advantages of diagnostic procedures while lowering the possibility of needless medical intervention.36Women who do not have a history of cervical cancer or significant precancerous lesions and who have had a complete hysterectomy (including cervix) for benign reasons should not be tested. Examining the Papanicolaou test’s effectiveness in detecting and monitoring cervical cytologic abnormalities. Most research on the traditional Pap test is blatantly biased. Based on the best estimations, it is only moderately accurate and does not reach high sensitivity and specificity at the same time. Pap test sensitivity estimates should be more cautious in cost-effectiveness models of cervical cancer screening.
|
Table-4: In accordance with the recommendations for their age group, women who have had an HPV vaccination should maintain screening |
|
|
Improving the Pap test's diagnostic accuracy |
Avoid taking a shower, having sex, or during menstruation. It is recommended to refrain from using tampons, local contraceptives, or other vaginal items 48 hours before to the Pap test. |
|
Women who test positive for HPV but have negative cytology
|
The American Society for Colposcopy and Cervical Pathology (ASCCP) screening guidelines state that women who test positive for HPV but have negative cytology should either be offered immediate HPV genotype-specific testing for HPV 16 alone or HPV 16 and 18 or repeat co-testing in a year. Women should be sent for a colposcopy if their immediate HPV genotyping returns a positive result for HPV 16 or HPV 18/18. Only for the treatment of women with a positive HPV test and negative cytology is it advised to employ HPV genotype-specific testing for HPV 16 alone or for both HPV 16 and 18. Additional than HPV, there is currently insufficient evidence to justify the use of additional biomarkers. |
|
Women with negative HPV test results and ASCUS cytology
|
Based on age-specific recommendations, women with ASCUS cytology and negative HPV test results should continue screening. |
|
Women over 65
|
Women over 65 who have had a negative previous screening result and have not had a CIN 2 history in the last 20 years should not undergo any kind of cervical cancer screening. Even if a woman reports having a new sexual partner, screening should never be repeated after it has been stopped. Three consecutive negative cytology results or two consecutive negative cytology and negative HPV testing findings within the ten years prior to screening ceasing, with the most recent screening occurring within the last five years, are considered satisfactory negative prior screening. |
|
Women over 65 having a history of adenocarcinoma in situ, CIN2, or CIN3:
|
Women should resume routine screening for at least 20 years following the spontaneous remission or proper treatment of CIN 2 and CIN 3 lesions or adenocarcinoma in situ (AIS) (even if screening is prolonged to past age 65 |
Numerous techniques, such as visual inspection with acetic acid (VIA), magnified VIA (VIAM), visual inspection with Lugol's iodine (VILI), the Papanicolaou test, and HPV DNA testing, can be used to screen for cervical cancer. Table 3 provides a concise summary of each screening modality's advantages and disadvantages. [9, 10, 11, 12, 13, 14, 15, 15] Important conclusions from Indian research
Table 5: cervical cancer screening tests along with strength and limitations.
|
Screening test |
Strengths |
Limitations |
|
VIA Acetic acid is applied to the cervix to identity precancerous and cancerous lesions |
Require less training (5-10days) than other methods Cheaper than cytology /HPV testing Immediate results Potential for immediate Treatment (“screen and treat”) |
Variable (low to moderate) sensitivity and specificity for CIN2+ Possibility for overtreatment Acetic acid must be prepared directly before screening Inappropriate for older women (more than 50 years) because of change in cervix position |
|
VIAM After application of acetic acid cervix is viewed under low magnification (x2-40) |
Same as VIA |
Magnification does not improve the test performance over and above that of naked-eye visualization |
|
VILI Lugol's iodine is applied to the cervix to identify precancerous and cancerous lesions. Process is often aided by a magnification tool |
Requires less training (between 5-10 days) than other methods Cheaper than cytology/HPV testing Immediate results Potential for immediate treatment ("screen and treat") Has as month shelf life |
Variable (low to moderate) sensitivity and specificity for CIN2+ Possibility for overtreatment |
|
Cytology (Papanicolaou smear) Sample of cells taken from transformational zone of the cervix. Sample is smeared onto a glass slide. Slide is sent to laboratory for reading by a cytologist |
High specificity for CINa+ |
Relatively low sensitivity Requires laboratory and specialized technicians Lag in test results can contribute to loss to follow-up and delay treatment Long duration of training of cytotechnicians (22- 24 months) |
|
HPV DNA test Sample of cells taken from the cervix by a provider or the woman herself. Sample is sent to laboratory for analysis by trained technicians |
High specificity and sensitivity for HPV infection Requires minimal training Woman can self-collect sample |
Has to be followed by a test for dysplasia Requires laboratory and trained technicians Lag in test results can contribute to loss to follow-up and delay treatment Costlier as compared to other methods |
|
CIN-Cervical intraepithelial neoplasia: VIA-Visual inspection with acetic acid, HPV-Human papilomavina, VWAM-Visual inspection with magnification, VILI-Visual inspection with Lugol's iodine |
||
There is enough data from Indian research to conclude that cervical cancer screening with a straightforward test like the VIA/VILI is practical, inexpensive, and an accurate method that can be used in all healthcare settings. Additionally, VIA/VILI offers the chance to use the "see and treat" strategy, which is advantageous in nations with limited resources and subpar follow-up. Additionally, grassroots health workers may be quickly trained to provide these tests, which will aid in the implementation of the screening program in rural locations. Nevertheless, high coverage rates and the capacity to treat test-positive women efficiently are critical components of any successful cervical screening program, in addition to the use of a valid and accurate screening test. It was discovered that the combined sensitivity and specificity for VIA were 67.65% and 84.32%, for VIAM they were 65.36% and 85.76%, and for VILI they were 78.27% and 87.10%. For HPV, the pooled sensitivity and specificity were 77.81% and 91.54%, respectively, while for cytology positive at the low-grade squamous intraepithelial neoplasia threshold, they were 62.11% and 93.51%.40
Figure 3: 5 years observation of survival rate in percentage by various stages of cancer
Figure 3 displays the survival rates of factors that are clinically significant. The stage of the illness was a significant variable that revealed variations in survival rates. With increasing illness severity, survival rates declined, with Stage IV exhibiting the lowest rates [Figure 1]. Differences in 5-year survival rates between illness stages were statistically significant, with Stage I, Stage II, Stage III, and Stage IV having respective 5-year survival rates of 84.4%, 80.3%, 65.9%, and 37.1%
Figure 4: 5 years observation of survival rate in percentage by various type of treatments
Figure 4 only 1562 (93.1%) of the patients that finished therapy were taken into account for analysis. Figure 2 illustrates that patients who received surgery alone (95.6%) or in conjunction with radiotherapy (90.6%) had the best results; patients who received surgery plus chemotherapy (87.7%) or both radiotherapy and chemotherapy (85.5%) had comparable results, although the rates were lower for those who received radiotherapy and chemotherapy (76.6%); and patients who received chemotherapy alone (15.9%) had the worst prognosis. The most popular treatment, either by itself or in conjunction with other forms of therapy, was radiotherapy. The survival rates of the various therapies were significantly different (P < 0> 41
Screening and Diagnosis
The HPV test and the Papanicolaou test are the two diagnostic test types available today for cervical cancer screening. The first one finds precancerous and cancerous cell lesions early so they may be treated successfully, while the second one finds HPV infections that can cause cancer.42 The current gold standard for HPV identification is molecular detection of HPV DNA or RNA. There are three types of molecular assays that can be used to detect HPV infection in tissue and exfoliated cell samples. These assays are all based on the detection of HPV DNA and include target amplification assays like polymerase chain reaction (PCR) and in situ PCR following are mention.
PCR based HPV detection
Real-time PCR is a variation of traditional PCR that yields more accurate quantitative data on amplified DNA quantities. Any nucleic acid sequence found in a sample may be amplified cyclically to produce several identical copies, which can then be examined. PCR is defined by a sequence of cycles at various temperatures that enable the target DNA molecules to get denaturated, certain primers to hybridize, and the Thermus aquaticus (Taq) polymerase to elongate the chain. Each cycle can be performed 20–40 times and has three steps. The simplest method for identifying a PCR product is to track the reaction's development constantly without stopping it to see the result on a gel.43
Signal amplified hybridization assays like
HPV detection with PCR is incredibly sensitive and specific. Moreover, reverse transcriptase (RT) PCR or nucleic acid sequence based amplification (NASBA) can be used to identify HPV E6/E7 mRNA and the existence of carcinogenic activity in cervical tissues. A nucleic acid hybridization assay with signal amplification using microplate chemiluminescence for semi-quantitative detection of HPV DNA in cervical specimens, the HC2 test detects at least 13 carcinogenic HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68). Single-stranded nucleic acids or RNA equivalents (such as viral genomic RNA, mRNA, or rRNA) are amplified against a double-stranded DNA background in NASBA tests.44 These days, the US Food and Drug Administration (FDA) have authorized three tests based on DNA and one based on RNA for regular cervical cancer screening. The Cervista HPV HR test (CER; Hologic, Madison, WI), the Cobas® HPV test (Roche, Pleasanton, USA), the Digene Hybrid Capture 2 High-Risk HPV DNA test (HC2; Qiagen, Hilden, Germany), and the RNA-based Aptima® HPV assay (Hologic, San Diego, CA) are a few of these.45–47 Cervista HPV HR test finds putative HR HPV type 66 in addition to the 13 carcinogenic HPV strains identified by HC2. The primers used in the Cobas 4800HPV PCR master mix amplify a 200-base pair region in the HPV genome's L1 polymorphism region. In contrast to the HPV 16, 18, and beta-globin signals, which are each identified with three distinct spectrally unique fluorescent labels, the fluorescence signal from the 12 HR kinds of HPV (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) is detected using the same fluorescent label. HPV 16 and 18 amplicon may be genotyped simultaneously apart from the other 12 HR types thanks to the unique distinctive wavelengths that define each label.48
Vaccination
Regarding vaccination, there are three options available to prevent infection with various HPV strains known to cause cervical cancer: shots of Gardasil and Gardasil 9 are administered in three doses at 0, 2, and 6 months; however, it was recently authorized to provide just two shots at 0 and 6 months to young girls under the age of 15. Cervarix must be taken in three doses (0, 1, and 6 months) and is also delivered via injection.49 Over 90% of cervical precancers and malignancies are probably preventable with HPV vaccination between the ages of 9 and 12.50 These commercial vaccines, which are made of the L1 capsid protein packaged as virus-like particles (VLPs), cause neutralizing antibodies that prevent the virus from infecting cervical epithelial cells. Even while major phase III studies in young women showed effectiveness of over 90%, vaccine scientists are currently focusing on more general concerns such producing cross-reactive antibodies for carcinogenic non-vaccine HPV strains, efficacy in boys, and duration of protection.
There are many organizations that work for cancer patients in India, including:
1. PRESCRIP TEC- (prevention screening innovation project towards elimination of cervical cancer)
PRESCRIP-TEC is related to the HPV self-test in which women perform the self-test using a cotton swab and then it is sent to the laboratory for further analysis. If the woman is found to have HPV she is called for screening. With VIA method (the See & Treat method) is performed by a health worker and with aid of the app (with AI) helps the health worker to recognize the discoloration of the cervix. Then on the spot women are treated right away.
2. Indian Cancer Society
Founded in 1951, this NGO provides support to cancer patients, including early detection, financial aid, rehabilitation, and counseling. They also run a cancer registry that provides data on cancer occurrence.
3. Global Cancer Concern India (GCCI)
This NGO provides free cancer screening camps, mobile palliative home care services, and vocational training for family members. They also have a Child Sponsorship Program to help with school fees.
4. VCARE Foundation
This organization provides counseling services, distributes cancer-related books, and organizes cancer survivor days.
5. JASCAP
This organization provides financial support to poor patients and maintains a books corner with cancer awareness booklets.
6. Cancer Patients Aid Association
This organization provides nutritional supplements to patients and participates in national festival celebrations.
7. Make a Wish Foundation
This organization identifies and fulfils the wishes of pediatric patients.
8. Mahindra Foundation
This organization provides kits to post-operative breast cancer patients.
9. Vasantha Memorial Trust
This organization provides counseling to cancer patients and their relatives.
10. Madat Charitable Trust
This organization provides counseling to cancer patients and their relatives, financial assistance, and wigs.
Summary
Cervical cancer may be mainly avoided with routine screening and follow-up. In low- and middle-income nations without organized screening and HPV vaccination programs, around 90% of cervical cancer cases occur. Since the implementation of official screening programs thirty years ago, the incidence and death of cervical cancer have more than halved in high-income nations. For women with low-risk, early-stage illness, conservative, fertility-preserving surgical techniques are now considered standard of care. Although the general prognosis for women with recurrent or metastatic cancer is still dismal, overall survival has been extended beyond 12 months with the use of bevacizumab, an anti-VEGF drug. As with other solid tumors, the first outcomes of innovative immunotherapeutic methods have been encouraging thus far.51
Future perspective
Better follow-up testing and treatment were the outcomes of the least expensive techniques, which also needed the fewest visits. By using a one- or two-visit screening strategy that involves visual inspection of the cervix with acetic acid or DNA testing for human papillomavirus (HPV) in cervical cell samples, screening women once in their lifetime, at the age of 35, decreased their lifetime risk of developing cancer by about 25 to 36 percent and saved lives.
CONCLUSION
Women who get screened once after the age of 35 have a 70% lower chance of dying from cervical cancer. Screening for cervical cancer every five years reduces her chance of death by almost 85%. The new technologies mentioned above provide a means of achieving this difficult objective.
REFERENCES
Shweta Gadekar*, Tejaswini Bhadake, Dr. Gajanan Sanap, Review on Cervical Cancer, Associate Risk, Staging, Screening Tests, Therapies and Vaccination, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 12, 3348-3365. https://doi.org/ 10.5281/zenodo.14575154
10.5281/zenodo.14575154
