Computer model for identification of groups of risk for malignant neoplasms of fe-male sex sphere using questionnaire

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Malignant neoplasms (MN) of the female sex sphere (FSS) are the second most common neoplastic disease (19.1%) after the breast cancer (20.9%). Mortality rate from cervical cancer in the Yaroslavl region (YR) in 2018 made 4%, from endometrium cancer – 5.3%, from ovarian cancer – 7.5% (per 100 000 of population) [1]. The causes of high mortality rate are late identification of the diseasesbecause of long-term asymptomatic course and difficulties of identification of MN in the preclinical period, late seeking for medical care, absence of mass screening for endometrial and ovarian cancer, low oncological alertness of primary care physicians and of patients [2-4].

The golden standard of early diagnosis of MN is identification of tumors in the preclinical stage through formation of dispensary groups and their annual examination in the preclinical period [4-6]. However, most primary care physicians do not create dispensary groups of risk, one of reasons for which beingthe absence of automation of questionnaire-laboratory scree-ning [7, 8].

At present there is no system of questionnaire screening in the practical healthcare system for formation of dispensary groups of risk for endometrial, cervical and ovarian cancer [9, 10]. Questionnaire screening of Russian women does not provide evaluation of statistically significant risk factors for MN of FSS with modern mathematical methods.

Aim – to identify statistically significant predictors of MN on the basis of multifactorial analysis of the results of questionnaire screening of conventionally healthy women and women with MN of female sex sphere that could help develop a computer program for formation of groups of risk for regular medical observation without participation of a physician.

Materials and Methods

The work was conducted on the basis of statistical processing of the data of questioning of 226 women divided to two groups: with MN of FSS (n=125) and conventionally healthy women (n=101), by a method of creation of a multifactorial model. Besides the questionnaire data, in the work materials of medical histories of patients and the data of histological research were used.

The data were analyzed using Statistica 10.0 (Stat Soft Inc., USA) and MedCalc1 2.7.0 (MedCalc Software, Belgium) programs. Multifactorial statistical analysis was applied. The quality of prediction of the studied phenomenon by predictors of MN of FSS was determined using ROC-analysis. The probability for development of MN of FSS on the basis of the most significant predictors was verified using statistical modeling. The method was described earlier in more detail [2, 11].

Results and Discussion

In result of the conducted analysis it was found that a statistically significant risk factor in the block of individual characteristics of patients was age (p<0.0001). The most important risk factors in the block of questions concerning sex function and ways of contraception were: late age for starting sex life – after 22 years (p=0.0002), installation of intrauterine spiral (IUS) in life (p=0.0164), and also a history of abortions (p<0.0001).

Among clinical manifestations of the disease, the most significant predictors of MN were bleeding from the genital tract (BGT) (p<0.0001) and a sharp loss of weight (LW) before the diagnosis. Analysis of questions concerning the way of life and the type of occupation showed that patients with MN more commonly had occupations associated with hard physical labor (p=0.0023), and more of them were living for a long time in military garrisons of air defense forces (ADF) (p=0.0086). Active way of life (AWL) was more common among conventionally healthy women (p=0.0576), while stresses, mental overloads (PS) were prevailing in the group of women with MN of FSS(p=0.0001).

Analysis of the block of questions about the existence of genital and extragenital diseases in women revealed the most common predomination of menstrual cycle disorders (MCD) (p=0.0011), of uterine myoma (UM) (p=0.0231), diabetes mellitus (DM) (p=0.0003), and also of cardiovascular diseases (CVD) (p<0.0001) in the group of women with MN of FSS. Besides, women with MN of FSS had problems with conception (p=0.0057), and in deliveries they had a higher incidence of cervical traumas in the form of ruptures (p=0.0006).

A block of questions concerning heredity revealed a higher incidence of breast cancer (p=0.0007) and cancer of other localization (p=0.0135) in relatives of patients with MN of FSS.

It should be noted that questions concerning diagnostics and awareness of women of prevention and diagnosis of MN of FSS, and their oncological alertness, demonstrated tactical mistakes of doctors: 85% of women with MN were not aware of methods of their prevention and of early diagnostics, while 65% women of the healthy group possessed this information (p<0.0001). The question ‘Do you have the Internet at home so thatcould you enter the site of our clinic to answer the questionnaire?’ was answered negatively by 67% of women. We think that this result shows the necessity for organization of computer places in women’s health clinics for questioning of women in the electronic network of medico-prophylactic institutions.

Finally, on the basis of application of multifactorial statistical ROC-analysis of 82 questions and answers of women, 18 statistically significant predictors of MN of FSS were identified that can be used to form groups of risk:

1. Age (A) (p<0.0001);
2. Menstrual cycle disorders (MCD) (p=0.0011);
3. Late start of sexual life (LSSL) (p=0.0002);
4. Existence of intrauterine spiral in life (IUS) (p=0.0164);
5. Active way of life with a negative coefficient (AWL) (p=0.0576);
6. Abortions in history (Ab) (p<0.0001);
7. Rupture of uterine cervix in deliveries (RUC) (p=0.0006);
8. Existence of uterine myoma (UM) (p=0.0231);
9. Occupation associated with a hard physical labor (HPL) (p=0.0023);
10. Loss of weight before diagnosis (LW) (p<0.0001);
11. Long-term living in garrisons of air
    defense forces (ADF) (p=0.0086);
12. Problems with conception (PC) (p=0.0057);
13. Psychological stresses, rueful feelings (PS) (p=0.0001);
14. Bleeding from genital tracts before diagnosis (BGT) (p<0.0001);
15. Existence of diabetes mellitus (DM) (p=0.0003);
16. Existence of cardiovascular diseases (CVD) (p<0.0001);
17. Breast cancer in relatives (BC in R) (p=0.0007);
18. Cancer of other localization in relatives (OC in R) (p=0.0135).

Results of ROC-analysis are given in Figure 1. The statistically significant level was p≤0.0001. The surface area below ROC-curve was 0.902; standard error – 0.0199; percentage of correctly classified cases – 72.8% (indicated confirmation of MN of FSS in 73 cases).

Measure of value and coordinate of ROC-curve were all meanings > 0.3267 with sensiti-vity 72.8% and specificity 95.0% (Figure 2).

 

Fig. 1. Forecasting of malignant neoplasms of female sex sphere using questioning

Note: surface area under ROC-curve was 0.902; AC – associated, or prognostic coefficient

 

Fig. 2. Associated coefficient (АC)

Note: measure of value and coordinate of ROC-curve were all meanings > 0.3267 with sensitivity 72.8% and specificity 95.0%

 

These parameters reflect the chances to make a correct diagnosis in ill and healthy individuals. Sensitivity was determined as a share of patients having a real disease among those with a positive test. Specificity was determined as a share of individuals having no disease among those with a negative test. Correlations of development of MN of FSS with the identified statistically significant risk factors are given in Table 1.

 

Table 1 Сorrelation of development of MN of FSS with identified statistically significant risk factors

Related Signs	Correlation Coefficient (R)	p
MN of FSS – abortions in history	0.2772	p<0.0001
MN of FSS – active way of life	-0.1274	p=0.0576
MN of FSS – IUS installed  in life	0.1605	p=0.0164
MN of FSS –living in garrisons of air defense troops	0.1755	p=0.0086
MN of FSS – age	0.6009	p<0.0001
MN of FSS – other cancers in relatives	0.1651	p=0.0135
MN of FSS – bleeding from genital tract before diagnosis	0.3478	p<0.0001
MN of FSS – uterine myoma	0.1521	p=0.0231
MN of FSS – late start of sexual life	0.2438	p=0.0002
MN of FSS – disorders in menstrual cycle	-0.2164	p=0.0011
MN of FSS – problems with conception	-0.1876	p=0.0057
MN of FSS – occupation associated with hard physical labor	0.2030	p=0.0023
MN of FSS – ruptures of uterine cervix in deliveries	0.2482	p=0.0006
MN of FSS – reduction of body mass before diagnosis	0.3805	p<0.0001
MN of FSS – breast cancer in relatives	0.2246	p=0.0007
MN of FSS – diabetes mellitus	0.2376	p=0.0003
MN of FSS – cardiovascular diseases	0.4514	p<0.0001
MN of FSS – stresses, rueful feelings, overloads	0.2677	p=0.0001

 

Logit regression of development of MN of FSS with the identified statistically significant risk factors is given in Table 2.

 

Table 2 Logit regression of development of malignant tumors of female sex sphere with identified statistically significant risk factors

Risk Factors	Coefficient	Standard Error	p
MN of FSS – – abortions in history	0,04823	0,5660	0,9321
MN of FSS – active way of life	-1,0828	0,6831	0,1129
MN of FSS – IUS installed  in life	-0,1923	0,5906	0,7447
MN of FSS  –living in garrisons of air defense troops	18,8194	2331,9512	0,9936
MN of FSS – age	0,05850	0,02747	0,0332
MN of FSS – other cancers in relatives	0,2615	0,8336	0,7538
MN of FSS  – bleeding from genital tract before diagnosis	1,2056	0,5774	0,0368
MN of FSS – uterine myoma	-0,3486	0,5670	0,5387
MN of FSS – late start of sexual life	0,1386	0,1532	0,3654
MN of FSS – disorders in menstrual cycle	-0,1036	0,6001	0,8629
MN of FSS – problems with conception	-2,0947	1,0903	0,0547
MN of FSS – occupation associated with hard physical labor	0,7483	0,6909	0,2788
MN of FSS – ruptures of uterine cervix in deliveries	1,7209	0,6463	0,0077
MN of FSS – reduction of body mass before diagnosis	1,6171	0,8248	0,0499
MN of FSS – breast cancer in relatives	1,2262	0,8590	0,1534
MN of FSS  – diabetes mellitus	0,8841	1,2704	0,4865
MN of FSS – cardiovascular diseases	0,5632	0,6828	0,4095
MN of FSS – stresses, rueful feelings, overloads	0,7538	0,6463	0,2435
Constant	-6,6071

 

On the basis of mathematical processing of the results according to R. Fischer method, normative signs were obtained, and amethod was formed for prognosis of MN of female sex sphere based on determination of prognostic coefficient (PC or AC) according to the formula developed by us:

 

PC = -6.6071 + (0.04823*Аb) + (-1.0828*AWL) +(-0.1923*IUS) + (18.8194*ADF) + (0.0585*A)  +(0.2615*OC in R) + (1.2056*BGT) + (-0.3486*UM) + (0.1386*LSSL) + (-0.1036*(MCD) + (-2.0947*PC) + (0.7483*HPL) + (1.7209*RUC) + (1.6171*LW) + (1.2262*BC in R) + (0.8841*DM) + (0.5632*CVD) + (0.7538*PS).

 

PC values below 0.3267 forecasts a low risk; PC values 0.3267 and above forecast a higher risk for development of MN of FSS [11].

Conclusion

Thus, multifactorial statistical ROC-analysis of 82 questions and answers of surveyed women (n=226) permitted to identify 18 statistically significant predictors of malignant neoplasms of female sex sphere which may substantiate formation of groups of risk to be covered by regular prophylactic examinations.

A formula was derived for calculation of prognostic (associated) coefficient with sensitivity 72.8% and specificity 95.0%

Besides, the obtained results were used for creation of a computer program and development of an automated system for testing on the Internet sites of hospitals and polyclinics. Introduction of questionnaire screening through the Internet with subsequent computer processing without direct participation of physicians will permit them to give more time for reception of primary patients, and also to raise oncological alertness of female population of the RF.

About the authors

Viktor N. Malashenkо

Yaroslavl State Medical University

Email: vestnik@rzgmu.ru
SPIN-code: 4229-9481

MD, PhD, Professor, Head of the Department of Oncology with Hematology

Russian Federation, Yaroslavl

Alexey M. Ershov

Yaroslavl State Medical University

Author for correspondence.
Email: alesha95951@mail.ru
ORCID iD: 0000-0002-4166-479X
SPIN-code: 1988-0031

Resident

Russian Federation, Yaroslavl

Yulia V. Ershova

Yaroslavl State Medical University

Email: vestnik@rzgmu.ru
ORCID iD: 0000-0003-4328-9150
SPIN-code: 9484-9860

MD, PhD, Associate Professor of the Department of Obstetrics and Gynecology

Russian Federation, Yaroslavl

References

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